Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)Amyloid beta-Peptides: Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.tau Proteins: Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).Amyloid beta-Protein Precursor: A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) UBIQUITINS. As one of the hallmarks of ALZHEIMER DISEASE, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease.Plaque, Amyloid: Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Apolipoprotein E4: A major and the second most common isoform of apolipoprotein E. In humans, Apo E4 differs from APOLIPOPROTEIN E3 at only one residue 112 (cysteine is replaced by arginine), and exhibits a lower resistance to denaturation and greater propensity to form folded intermediates. Apo E4 is a risk factor for ALZHEIMER DISEASE and CARDIOVASCULAR DISEASES.Amyloid Precursor Protein Secretases: Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.Cognition Disorders: Disturbances in mental processes related to learning, thinking, reasoning, and judgment.Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.Presenilin-1: Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.Amyloid: A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Dementia, Vascular: An imprecise term referring to dementia associated with CEREBROVASCULAR DISORDERS, including CEREBRAL INFARCTION (single or multiple), and conditions associated with chronic BRAIN ISCHEMIA. Diffuse, cortical, and subcortical subtypes have been described. (From Gerontol Geriatr 1998 Feb;31(1):36-44)Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury.Neurofibrils: The delicate interlacing threads, formed by aggregations of neurofilaments and neurotubules, coursing through the CYTOPLASM of the body of a NEURON and extending from one DENDRITE into another or into the AXON.Mild Cognitive Impairment: A prodromal phase of cognitive decline that may precede the emergence of ALZHEIMER DISEASE and other dementias. It may include impairment of cognition, such as impairments in language, visuospatial awareness, ATTENTION and MEMORY.Apolipoproteins E: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.Presenilin-2: Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN2 mutations cause ALZHEIMER DISEASE type 4.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Mental Status Schedule: Standardized clinical interview used to assess current psychopathology by scaling patient responses to the questions.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Cognition: Intellectual or mental process whereby an organism obtains knowledge.Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques.Lewy Body Disease: A neurodegenerative disease characterized by dementia, mild parkinsonism, and fluctuations in attention and alertness. The neuropsychiatric manifestations tend to precede the onset of bradykinesia, MUSCLE RIGIDITY, and other extrapyramidal signs. DELUSIONS and visual HALLUCINATIONS are relatively frequent in this condition. Histologic examination reveals LEWY BODIES in the CEREBRAL CORTEX and BRAIN STEM. SENILE PLAQUES and other pathologic features characteristic of ALZHEIMER DISEASE may also be present. (From Neurology 1997;48:376-380; Neurology 1996;47:1113-1124)Memantine: AMANTADINE derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent.Age of Onset: The age, developmental stage, or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual.Presenilins: Integral membrane proteins and essential components of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. Mutations of presenilins lead to presenile ALZHEIMER DISEASE with onset before age 65 years.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Aniline CompoundsNeurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.National Institute on Aging (U.S.): Component of the NATIONAL INSTITUTES OF HEALTH. Through basic and clinical biomedical research and training, it conducts and supports research into the nature of the aging process and diseases associated with the later stages of life. The Institute was established in 1974.Substantia Innominata: Tissue in the BASAL FOREBRAIN inferior to the anterior perforated substance, and anterior to the GLOBUS PALLIDUS and ansa lenticularis. It contains the BASAL NUCLEUS OF MEYNERT.Memory Disorders: Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.Cerebral Cortex: The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.Cerebral Amyloid Angiopathy: A heterogeneous group of sporadic or familial disorders characterized by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES. Clinical features include multiple, small lobar CEREBRAL HEMORRHAGE; cerebral ischemia (BRAIN ISCHEMIA); and CEREBRAL INFARCTION. Cerebral amyloid angiopathy is unrelated to generalized AMYLOIDOSIS. Amyloidogenic peptides in this condition are nearly always the same ones found in ALZHEIMER DISEASE. (from Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., 2005)Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time.Amyloidogenic Proteins: Proteins that form the core of amyloid fibrils. For example, the core of amyloid A is formed from amyloid A protein, also known as serum amyloid A protein or SAA protein.Autopsy: Postmortem examination of the body.Brain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.Positron-Emission Tomography: An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Nerve Degeneration: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.Protease Nexins: Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.Prodromal Symptoms: Clinical or physiological indicators that precede the onset of disease.Phenylcarbamates: Phenyl esters of carbamic acid or of N-substituted carbamic acids. Structures are similar to PHENYLUREA COMPOUNDS with a carbamate in place of the urea.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Tauopathies: Neurodegenerative disorders involving deposition of abnormal tau protein isoforms (TAU PROTEINS) in neurons and glial cells in the brain. Pathological aggregations of tau proteins are associated with mutation of the tau gene on chromosome 17 in patients with ALZHEIMER DISEASE; DEMENTIA; PARKINSONIAN DISORDERS; progressive supranuclear palsy (SUPRANUCLEAR PALSY, PROGRESSIVE); and corticobasal degeneration.Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.Indans: Aryl CYCLOPENTANES that are a reduced (protonated) form of INDENES.Nootropic Agents: Drugs used to specifically facilitate learning or memory, particularly to prevent the cognitive deficits associated with dementias. These drugs act by a variety of mechanisms. While no potent nootropic drugs have yet been accepted for general use, several are being actively investigated.Down Syndrome: A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Lewy Bodies: Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of Lewy bodies is the histological marker of the degenerative changes in LEWY BODY DISEASE and PARKINSON DISEASE but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex.Clioquinol: A potentially neurotoxic 8-hydroxyquinoline derivative long used as a topical anti-infective, intestinal antiamebic, and vaginal trichomonacide. The oral preparation has been shown to cause subacute myelo-optic neuropathy and has been banned worldwide.ThiazolesFrontotemporal Dementia: The most common clinical form of FRONTOTEMPORAL LOBAR DEGENERATION, this dementia presents with personality and behavioral changes often associated with disinhibition, apathy, and lack of insight.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Amnesia: Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7)Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Temporal Lobe: Lower lateral part of the cerebral hemisphere responsible for auditory, olfactory, and semantic processing. It is located inferior to the lateral fissure and anterior to the OCCIPITAL LOBE.Psychomotor Agitation: A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions.Nerve Tissue ProteinsNeuropil Threads: Abnormal structures located chiefly in distal dendrites and, along with NEUROFIBRILLARY TANGLES and SENILE PLAQUES, constitute the three morphological hallmarks of ALZHEIMER DISEASE. Neuropil threads are made up of straight and paired helical filaments which consist of abnormally phosphorylated microtubule-associated tau proteins. It has been suggested that the threads have a major role in the cognitive impairment seen in Alzheimer disease.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Insulysin: An enzyme the catalyzes the degradation of insulin, glucagon and other polypeptides. It is inhibited by bacitracin, chelating agents EDTA and 1,10-phenanthroline, and by thiol-blocking reagents such as N-ethylmaleimide, but not phosphoramidon. (Eur J Biochem 1994;223:1-5) EC 3.4.24.56.Apolipoprotein E3: A 34-kDa glycosylated protein. A major and most common isoform of apolipoprotein E. Therefore, it is also known as apolipoprotein E (ApoE). In human, Apo E3 is a 299-amino acid protein with a cysteine at the 112 and an arginine at the 158 position. It is involved with the transport of TRIGLYCERIDES; PHOSPHOLIPIDS; CHOLESTEROL; and CHOLESTERYL ESTERS in and out of the cells.Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders.Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.Chromosomes, Human, Pair 21: A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.Monomeric Clathrin Assembly Proteins: A subclass of clathrin assembly proteins that occur as monomers.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.Parkinson Disease: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Apolipoprotein E2: One of three major isoforms of apolipoprotein E. In humans, Apo E2 differs from APOLIPOPROTEIN E3 at one residue 158 where arginine is replaced by cysteine (R158--C). In contrast to Apo E3, Apo E2 displays extremely low binding affinity for LDL receptors (RECEPTORS, LDL) which mediate the internalization and catabolism of lipoprotein particles in liver cells. ApoE2 allelic homozygosity is associated with HYPERLIPOPROTEINEMIA TYPE III.Kluver-Bucy Syndrome: A neurobehavioral syndrome associated with bilateral medial temporal lobe dysfunction. Clinical manifestations include oral exploratory behavior; tactile exploratory behavior; hypersexuality; BULIMIA; MEMORY DISORDERS; placidity; and an inability to recognize objects or faces. This disorder may result from a variety of conditions, including CRANIOCEREBRAL TRAUMA; infections; ALZHEIMER DISEASE; PICK DISEASE OF THE BRAIN; and CEREBROVASCULAR DISORDERS.Galantamine: A benzazepine derived from norbelladine. It is found in GALANTHUS and other AMARYLLIDACEAE. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of GALLAMINE TRIETHIODIDE and TUBOCURARINE and has been studied as a treatment for ALZHEIMER DISEASE and other central nervous system disorders.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Frontotemporal Lobar Degeneration: Heterogeneous group of neurodegenerative disorders characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Multiple subtypes or forms are recognized based on presence or absence of TAU PROTEIN inclusions. FTLD includes three clinical syndromes: FRONTOTEMPORAL DEMENTIA, semantic dementia, and PRIMARY PROGRESSIVE NONFLUENT APHASIA.Benzothiazoles: Compounds with a benzene ring fused to a thiazole ring.Genetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Neurocalcin: A neuronal calcium sensor protein that is expressed as several isoforms and can interact with ACTIN; TUBULIN; and CLATHRIN.Amyloidosis: A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.LDL-Receptor Related Proteins: A family of proteins that share sequence similarity with the low density lipoprotein receptor (RECEPTORS, LDL).CA2 Region, Hippocampal: A subsection of the hippocampus, described by Lorente de No, that is located between the HIPPOCAMPUS CA1 FIELD and the HIPPOCAMPUS CA3 FIELD.Nerve Fibers, Myelinated: A class of nerve fibers as defined by their structure, specifically the nerve sheath arrangement. The AXONS of the myelinated nerve fibers are completely encased in a MYELIN SHEATH. They are fibers of relatively large and varied diameters. Their NEURAL CONDUCTION rates are faster than those of the unmyelinated nerve fibers (NERVE FIBERS, UNMYELINATED). Myelinated nerve fibers are present in somatic and autonomic nerves.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.Caregivers: Persons who provide care to those who need supervision or assistance in illness or disability. They may provide the care in the home, in a hospital, or in an institution. Although caregivers include trained medical, nursing, and other health personnel, the concept also refers to parents, spouses, or other family members, friends, members of the clergy, teachers, social workers, fellow patients.Severity of Illness Index: Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder.Cyclin-Dependent Kinase 5: A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.Postmortem Changes: Physiological changes that occur in bodies after death.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Entorhinal Cortex: Cerebral cortex region on the medial aspect of the PARAHIPPOCAMPAL GYRUS, immediately caudal to the OLFACTORY CORTEX of the uncus. The entorhinal cortex is the origin of the major neural fiber system afferent to the HIPPOCAMPAL FORMATION, the so-called PERFORANT PATHWAY.Dominican Republic: A republic in the Greater Antilles in the West Indies. Its capital is Santo Domingo. With Haiti, it forms the island of Hispaniola - the Dominican Republic occupying the eastern two thirds, and Haiti, the western third. It was created in 1844 after a revolt against the rule of President Boyer over the entire island of Hispaniola, itself visited by Columbus in 1492 and settled the next year. Except for a brief period of annexation to Spain (1861-65), it has been independent, though closely associated with the United States. Its name comes from the Spanish Santo Domingo, Holy Sunday, with reference to its discovery on a Sunday. (From Webster's New Geographical Dictionary, 1988, p338, 506 & Room, Brewer's Dictionary of Names, 1992, p151)Frontal Lobe: The part of the cerebral hemisphere anterior to the central sulcus, and anterior and superior to the lateral sulcus.Clusterin: A highly conserved heterodimeric glycoprotein that is differentially expressed during many severe physiological disturbance states such as CANCER; APOPTOSIS; and various NEUROLOGICAL DISORDERS. Clusterin is ubiquitously expressed and appears to function as a secreted MOLECULAR CHAPERONE.Psychiatric Status Rating Scales: Standardized procedures utilizing rating scales or interview schedules carried out by health personnel for evaluating the degree of mental illness.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Age Factors: Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time.Image Processing, Computer-Assisted: A technique of inputting two-dimensional images into a computer and then enhancing or analyzing the imagery into a form that is more useful to the human observer.Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.PC12 Cells: A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.Astrocytes: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Maze Learning: Learning the correct route through a maze to obtain reinforcement. It is used for human or animal populations. (Thesaurus of Psychological Index Terms, 6th ed)Caribbean Region: The area that lies between continental North and South America and comprises the Caribbean Sea, the West Indies, and the adjacent mainland regions of southern Mexico, Central America, Colombia, and Venezuela.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98.PrPC Proteins: Normal cellular isoform of prion proteins (PRIONS) encoded by a chromosomal gene and found in normal and scrapie-infected brain tissue, and other normal tissue. PrPC are protease-sensitive proteins whose function is unknown. Posttranslational modification of PrPC into PrPSC leads to infectivity.Caspase 6: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Alzheimer Vaccines: Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Neurofilament Proteins: Type III intermediate filament proteins that assemble into neurofilaments, the major cytoskeletal element in nerve axons and dendrites. They consist of three distinct polypeptides, the neurofilament triplet. Types I, II, and IV intermediate filament proteins form other cytoskeletal elements such as keratins and lamins. It appears that the metabolism of neurofilaments is disturbed in Alzheimer's disease, as indicated by the presence of neurofilament epitopes in the neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit of the neurofilament triplet in brains of Alzheimer's patients. (Can J Neurol Sci 1990 Aug;17(3):302)Aphasia, Primary Progressive: A progressive form of dementia characterized by the global loss of language abilities and initial preservation of other cognitive functions. Fluent and nonfluent subtypes have been described. Eventually a pattern of global cognitive dysfunction, similar to ALZHEIMER DISEASE, emerges. Pathologically, there are no Alzheimer or PICK DISEASE like changes, however, spongiform changes of cortical layers II and III are present in the TEMPORAL LOBE and FRONTAL LOBE. (From Brain 1998 Jan;121(Pt 1):115-26)Prions: Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL.Lemur: A genus of the family Lemuridae consisting of five species: L. catta (ring-tailed lemur), L. fulvus, L. macaco (acoumba or black lemur), L. mongoz (mongoose lemur), and L. variegatus (white lemur). Most members of this genus occur in forested areas on Madagascar and the Comoro Islands.Fluorodeoxyglucose F18: The compound is given by intravenous injection to do POSITRON-EMISSION TOMOGRAPHY for the assessment of cerebral and myocardial glucose metabolism in various physiological or pathological states including stroke and myocardial ischemia. It is also employed for the detection of malignant tumors including those of the brain, liver, and thyroid gland. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1162)Family Health: The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.Protein Multimerization: The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.Cerebral Ventricles: Four CSF-filled (see CEREBROSPINAL FLUID) cavities within the cerebral hemispheres (LATERAL VENTRICLES), in the midline (THIRD VENTRICLE) and within the PONS and MEDULLA OBLONGATA (FOURTH VENTRICLE).Predictive Value of Tests: In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.Solubility: The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Proteolysis: Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Parahippocampal Gyrus: A convolution on the inferior surface of each cerebral hemisphere, lying between the hippocampal and collateral sulci.Congo Red: An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.Genome-Wide Association Study: An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Hypokinesia: Slow or diminished movement of body musculature. It may be associated with BASAL GANGLIA DISEASES; MENTAL DISORDERS; prolonged inactivity due to illness; and other conditions.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.alpha-Synuclein: A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.Hydrocephalus, Normal Pressure: A form of compensated hydrocephalus characterized clinically by a slowly progressive gait disorder (see GAIT DISORDERS, NEUROLOGIC), progressive intellectual decline, and URINARY INCONTINENCE. Spinal fluid pressure tends to be in the high normal range. This condition may result from processes which interfere with the absorption of CSF including SUBARACHNOID HEMORRHAGE, chronic MENINGITIS, and other conditions. (From Adams et al., Principles of Neurology, 6th ed, pp631-3)Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Blood-Brain Barrier: Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.Early Diagnosis: Methods to determine in patients the nature of a disease or disorder at its early stage of progression. Generally, early diagnosis improves PROGNOSIS and TREATMENT OUTCOME.Osteopathic Physicians: Licensed physicians trained in OSTEOPATHIC MEDICINE. An osteopathic physician, also known as D.O. (Doctor of Osteopathy), is able to perform surgery and prescribe medications.Huntington Disease: A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4)Cerebrovascular Circulation: The circulation of blood through the BLOOD VESSELS of the BRAIN.Ethylene Glycols: An ethylene compound with two hydroxy groups (-OH) located on adjacent carbons. They are viscous and colorless liquids. Some are used as anesthetics or hypnotics. However, the class is best known for their use as a coolant or antifreeze.Protein PrecursorsProtein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Neprilysin: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.Extrapyramidal Tracts: Uncrossed tracts of motor nerves from the brain to the anterior horns of the spinal cord, involved in reflexes, locomotion, complex movements, and postural control.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Cognitive Reserve: Capacity that enables an individual to cope with and/or recover from the impact of a neural injury or a psychotic episode.Immunotherapy, Active: Active immunization where vaccine is administered for therapeutic or preventive purposes. This can include administration of immunopotentiating agents such as BCG vaccine and Corynebacterium parvum as well as biological response modifiers such as interferons, interleukins, and colony-stimulating factors in order to directly stimulate the immune system.Neurites: In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell.Cerebrovascular Disorders: A spectrum of pathological conditions of impaired blood flow in the brain. They can involve vessels (ARTERIES or VEINS) in the CEREBRUM, the CEREBELLUM, and the BRAIN STEM. Major categories include INTRACRANIAL ARTERIOVENOUS MALFORMATIONS; BRAIN ISCHEMIA; CEREBRAL HEMORRHAGE; and others.Brief Psychiatric Rating Scale: A scale comprising 18 symptom constructs chosen to represent relatively independent dimensions of manifest psychopathology. The initial intended use was to provide more efficient assessment of treatment response in clinical psychopharmacology research; however, the scale was readily adapted to other uses. (From Hersen, M. and Bellack, A.S., Dictionary of Behavioral Assessment Techniques, p. 87)Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7.Mice, Inbred C57BLHEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Encephalitis: Inflammation of the BRAIN due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see ENCEPHALITIS, VIRAL) are a relatively frequent cause of this condition.

Alzheimer's disease: clues from flies and worms. (1/11292)

Presenilin mutations give rise to familial Alzheimer's disease and result in elevated production of amyloid beta peptide. Recent evidence that presenilins act in developmental signalling pathways may be the key to understanding how senile plaques, neurofibrillary tangles and apoptosis are all biochemically linked.  (+info)

Parametric mapping of cerebral blood flow deficits in Alzheimer's disease: a SPECT study using HMPAO and image standardization technique. (2/11292)

This study assessed the accuracy and reliability of Automated Image Registration (AIR) for standardization of brain SPECT images of patients with Alzheimer's disease (AD). Standardized cerebral blood flow (CBF) images of patients with AD and control subjects were then used for group comparison and covariance analyses. METHODS: Thirteen patients with AD at an early stage (age 69.8+/-7.1 y, Clinical Dementia Rating Score 0.5-1.0, Mini-Mental State Examination score 19-23) and 20 age-matched normal subjects (age 69.5+/-8.3 y) participated in this study. 99mTc-hexamethyl propylenamine oxime (HMPAO) brain SPECT and CT scans were acquired for each subject. SPECT images were transformed to a standard size and shape with the help of AIR. Accuracy of AIR for spatial normalization was evaluated by an index calculated on SPECT images. Anatomical variability of standardized target images was evaluated by measurements on corresponding CT scans, spatially normalized using transformations established by the SPECT images. Realigned brain SPECT images of patients and controls were used for group comparison with the help of statistical parameter mapping. Significant differences were displayed on the respective voxel to generate three-dimensional Z maps. CT scans of individual subjects were evaluated by a computer program for brain atrophy. Voxel-based covariance analysis was performed on standardized images with ages and atrophy indices as independent variables. RESULTS: Inaccuracy assessed by functional data was 2.3%. The maximum anatomical variability was 4.9 mm after standardization. Z maps showed significantly decreased regional CBF (rCBF) in the frontal, parietal and temporal regions in the patient group (P < 0.001). Covariance analysis revealed that the effects of aging on rCBF were more pronounced compared with atrophy, especially in intact cortical areas at an early stage of AD. Decrease in rCBF was partly due to senility and atrophy, however these two factors cannot explain all the deficits. CONCLUSION: AIR can transform SPECT images of AD patients with acceptable accuracy without any need for corresponding structural images. The frontal regions of the brain, in addition to parietal and temporal lobes, may show reduced CBF in patients with AD even at an early stage of dementia. The reduced rCBF in the cortical regions cannot be explained entirely by advanced atrophy and fast aging process.  (+info)

Proteolytic processing of the Alzheimer's disease amyloid precursor protein within its cytoplasmic domain by caspase-like proteases. (3/11292)

Alzheimer's disease is characterized by neurodegeneration and deposition of betaA4, a peptide that is proteolytically released from the amyloid precursor protein (APP). Missense mutations in the genes coding for APP and for the polytopic membrane proteins presenilin (PS) 1 and PS2 have been linked to familial forms of early-onset Alzheimer's disease. Overexpression of presenilins, especially that of PS2, induces increased susceptibility for apoptosis that is even more pronounced in cells expressing presenilin mutants. Additionally, presenilins themselves are targets for activated caspases in apoptotic cells. When we analyzed APP in COS-7 cells overexpressing PS2, we observed proteolytic processing close to the APP carboxyl terminus. Proteolytic conversion was increased in the presence of PS2-I, which encodes one of the known PS2 pathogenic mutations. The same proteolytic processing occurred in cells treated with chemical inducers of apoptosis, suggesting a participation of activated caspases in the carboxyl-terminal truncation of APP. This was confirmed by showing that specific caspase inhibitors blocked the apoptotic conversion of APP. Sequence analysis of the APP cytosolic domain revealed a consensus motif for group III caspases ((IVL)ExD). Mutation of the corresponding Asp664 residue abolished cleavage, thereby identifying APP as a target molecule for caspase-like proteases in the pathways of programmed cellular death.  (+info)

Microvessels from Alzheimer's disease brains kill neurons in vitro. (4/11292)

Understanding the pathogenesis of Alzheimer's disease is of widespread interest because it is an increasingly prevalent disorder that is progressive, fatal, and currently untreatable. The dementia of Alzheimer's disease is caused by neuronal cell death. We demonstrate for the first time that blood vessels isolated from the brains of Alzheimer's disease patients can directly kill neurons in vitro. Either direct co-culture of Alzheimer's disease microvessels with neurons or incubation of cultured neurons with conditioned medium from microvessels results in neuronal cell death. In contrast, vessels from elderly nondemented donors are significantly (P<0.001) less lethal and brain vessels from younger donors are not neurotoxic. Neuronal killing by either direct co-culture with Alzheimer's disease microvessels or conditioned medium is dose- and time-dependent. Neuronal death can occur by either apoptotic or necrotic mechanisms. The microvessel factor is neurospecific, killing primary cortical neurons, cerebellar granule neurons, and differentiated PC-12 cells, but not non-neuronal cell types or undifferentiated PC-12 cells. Appearance of the neurotoxic factor is decreased by blocking microvessel protein synthesis with cycloheximide. The neurotoxic factor is soluble and likely a protein, because its activity is heat labile and trypsin sensitive. These findings implicate a novel mechanism of vascular-mediated neuronal cell death in Alzheimer's disease.  (+info)

Specific regional transcription of apolipoprotein E in human brain neurons. (5/11292)

In central nervous system injury and disease, apolipoprotein E (APOE, gene; apoE, protein) might be involved in neuronal injury and death indirectly through extracellular effects and/or more directly through intracellular effects on neuronal metabolism. Although intracellular effects could clearly be mediated by neuronal uptake of extracellular apoE, recent experiments in injury models in normal rodents and in mice transgenic for the human APOE gene suggest the additional possibility of intraneuronal synthesis. To examine whether APOE might be synthesized by human neurons, we performed in situ hybridization on paraffin-embedded and frozen brain sections from three nondemented controls and five Alzheimer's disease (AD) patients using digoxigenin-labeled antisense and sense cRNA probes to human APOE. Using the antisense APOE probes, we found the expected strong hybridization signal in glial cells as well as a generally fainter signal in selected neurons in cerebral cortex and hippocampus. In hippocampus, many APOE mRNA-containing neurons were observed in sectors CA1 to CA4 and the granule cell layer of the dentate gyrus. In these regions, APOE mRNA containing neurons could be observed adjacent to nonhybridizing neurons of the same cell class. APOE mRNA transcription in neurons is regionally specific. In cerebellar cortex, APOE mRNA was seen only in Bergmann glial cells and scattered astrocytes but not in Purkinje cells or granule cell neurons. ApoE immunocytochemical localization in semi-adjacent sections supported the selectivity of APOE transcription. These results demonstrate the expected result that APOE mRNA is transcribed and expressed in glial cells in human brain. The important new finding is that APOE mRNA is also transcribed and expressed in many neurons in frontal cortex and human hippocampus but not in neurons of cerebellar cortex from the same brains. This regionally specific human APOE gene expression suggests that synthesis of apoE might play a role in regional vulnerability of neurons in AD. These results also provide a direct anatomical context for hypotheses proposing a role for apoE isoforms on neuronal cytoskeletal stability and metabolism.  (+info)

Increased phosphoglycerate kinase in the brains of patients with Down's syndrome but not with Alzheimer's disease. (6/11292)

Impaired glucose metabolism in Down's syndrome (DS) has been well-documented in vivo, although information on the underlying biochemical defect is limited and no biochemical studies on glucose handling enzymes have been carried out in the brain. Through gene hunting in fetal DS brain we found an overexpressed sequence homologous to the phosphoglycerate kinase (PGK) gene. This finding was studied further by investigating the activity levels of this key enzyme of carbohydrate metabolism in the brains of patients with DS. PGK activity was determined in five brain regions of nine patients with DS, nine patients with Alzheimer's disease and 14 controls. PGK activity was significantly elevated in the frontal, occipital and temporal lobe and in the cerebellum of patients with DS. PGK activity in corresponding brain regions of patients with Alzheimer's disease was comparable with controls. We conclude that our findings complement previously published data on impaired brain glucose metabolism in DS evaluated by positron emission tomography in clinical studies. Furthermore, we show that in DS, impaired glucose metabolism, represented by increased PGK activity, is a specific finding rather than a secondary phenomenon simply due to neurodegeneration or atrophy. These observations are also supported by data from subtractive hybridization, showing overexpressed PGK in DS brains at the transcriptional level early in life.  (+info)

Translation of the alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5'-untranslated region sequences. (7/11292)

The amyloid precursor protein (APP) has been associated with Alzheimer's disease (AD) because APP is processed into the beta-peptide that accumulates in amyloid plaques, and APP gene mutations can cause early onset AD. Inflammation is also associated with AD as exemplified by increased expression of interleukin-1 (IL-1) in microglia in affected areas of the AD brain. Here we demonstrate that IL-1alpha and IL-1beta increase APP synthesis by up to 6-fold in primary human astrocytes and by 15-fold in human astrocytoma cells without changing the steady-state levels of APP mRNA. A 90-nucleotide sequence in the APP gene 5'-untranslated region (5'-UTR) conferred translational regulation by IL-1alpha and IL-1beta to a chloramphenicol acetyltransferase (CAT) reporter gene. Steady-state levels of transfected APP(5'-UTR)/CAT mRNAs were unchanged, whereas both base-line and IL-1-dependent CAT protein synthesis were increased. This APP mRNA translational enhancer maps from +55 to +144 nucleotides from the 5'-cap site and is homologous to related translational control elements in the 5'-UTR of the light and and heavy ferritin genes. Enhanced translation of APP mRNA provides a mechanism by which IL-1 influences the pathogenesis of AD.  (+info)

Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. (8/11292)

Transgenic mice overexpressing different forms of amyloid precursor protein (APP), i.e. wild type or clinical mutants, displayed an essentially comparable early phenotype in terms of behavior, differential glutamatergic responses, deficits in maintenance of long term potentiation, and premature death. The cognitive impairment, demonstrated in F1 hybrids of the different APP transgenic lines, was significantly different from nontransgenic littermates as early as 3 months of age. Biochemical analysis of secreted and membrane-bound APP, C-terminal "stubs," and Abeta(40) and Abeta(42) peptides in brain indicated that no single intermediate can be responsible for the complex of phenotypic dysfunctions. As expected, the Abeta(42) levels were most prominent in APP/London transgenic mice and correlated directly with the formation of amyloid plaques in older mice of this line. Plaques were associated with immunoreactivity for hyperphosphorylated tau, eventually signaling some form of tau pathology. In conclusion, the different APP transgenic mouse lines studied display cognitive deficits and phenotypic traits early in life that dissociated in time from the formation of amyloid plaques and will be good models for both early and late neuropathological and clinical aspects of Alzheimer's disease.  (+info)

University of California Los Angeles (UCLA) Alzheimers Disease Research Center is one of leading Southern California Alzheimers Disease Research Centers(ADRC). Learn about early signs and symptoms on memory loss and last stages of Alzheimers disease and other dementias through one of the best Alzheimers Neurologists; how to delay the early onset Alzheimers disease and treatments on non-alzheimers dementias such as dementia with Lewy Bodies (DLB), vascular or multi-infarct dementia or frontotemporal dementia (FTD) which is also called Picks disease.
que es el Alzheimer? Alzheimers Disease Research Center at University of California, Los Angles (UCLA) also enrolls patients and subjects in clinical and pre-clinical research program. Alzheimers Disease NeuroImaging Initiative (ADNI) is a brain imaging and biomarkers, and longitudinal studies. We have bilingual staff that speaks Spanish and English. UCLA Alzheimers Disease Research Center is located in Los Angeles, California.
UCLA Alzheimers Disease Research Center at UCLA, Los Angeles, California is looking for clinical trial participants in medication and non-medication research studies for potential drugs to treat Alzheimers disease. Learn the causes, symptoms, risk factors, early onset, progression, treatments, stages related dementias and latest Alzheimers research break-through at the UCLA Alzheimers Disease Research Center.
University of California Los Angeles (UCLA) Alzheimers Disease Research Center is one of the leading Southern California Alzheimers Disease Research Centers(ADRC). Learn about early signs and symptoms on memory loss and Alzheimers disease and other dementias through one of the best Alzheimers Research Centers; how to delay the early onset Alzheimers diesease and treatments on non-alzheimers dementias such as dementia with Lewy Bodies (DLB), vascular or multi-infarct dementia or frontotemporal dementia (FTD) which is also called Picks disease.
The Michigan Alzheimers Disease Research Center will host its third annual "Beyond Amyloid" research symposium this summer.. All Michigan Medicine faculty and staff are invited to register for the event, which will take place on Wednesday, June 19 at the MSU College of Human Medicines Seccchia Center, located at 15 Michigan St. NE in Grand Rapids, Michigan.. The keynote speakers include Russel Swerdlow, M.D., director of the University of Kansas Alzheimers Disease Center, and Linda Van Eldik, Ph.D., director of the University of Kentucky Alzheimers Disease Center. Abstracts are also being accepted.. Learn more or register by clicking here.. ...
These findings suggest that the functional neuroanatomical alterations underlying explicit memory changes in mild Alzheimers disease differ from those seen with normal aging. Particularly striking was the fact that the regions showing the greatest decreases in activation in the patients with mild Alzheimers disease compared with the elderly controls were in the hippocampal formation. We hypothesise that this is the result of the extensive neuronal loss (in conjunction with neuritic plaques and neurofibrillary tangles) that develops early in the course of Alzheimers disease.3 It is likely that regional atrophy is also at least partially responsible for the decreased hippocampal activation in Alzheimers disease.16 However, this is unlikely to be the entire explanation for our findings, as we saw little evidence of paradigm linked activation in the hippocampus in six of the seven Alzheimer patients when the MR signal was sampled within a small section of the hippocampus, guided by each ...
HealthDay News) -- Alzheimers patients given sedatives such as Valium or Xanax may have an increased risk for pneumonia, a new study warns.. People with Alzheimers disease are often given these drugs, called benzodiazepines, over the long term, the researchers said.. Examples of benzodiazepines include alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), and lorazepam (Ativan).. An increased risk of pneumonia is an important finding to consider in treatment of patients with Alzheimer disease. Pneumonia often leads to admission to hospital, and patients with dementia are at increased risk of death related to pneumonia, Dr. Heidi Taipale, of Kuopio Research Center of Geriatric Care at the University of Eastern Finland, and co-authors wrote.. For the study, the researchers reviewed data from nearly 50,000 Alzheimers patients in Finland. The patients average age was 80 and about two-thirds were women.. The study found that people with Alzheimers who took benzodiazepines were 30 ...
Guided by the latest biomarker and imaging data, scientists have drafted a new set of diagnostic research criteria redefining Alzheimer disease as a condition that develops-and eventually could warrant intervention-decades prior to obvious symptoms. Most clinicians welcomed the changes, which were proposed last month at the International Conference on Alzheimers Disease (ICAD) in Honolulu, Hawaii, but some questioned the benefit of earlier diagnosis while there is yet no way to stop the disease in its tracks (see ARF related news story). Amid this debate looms the critical question of how well biomarkers can predict who among the cognitively normal is heading toward dementia and, eventually, full-blown AD. This report recaps a sampling of ICAD studies that address this issue. By and large, the data suggest that seniors who appear normal on cognitive tests, but nonetheless suspect their memory is off, or who have high brain amyloid or other pathological reads, may already be quietly on the ...
This study was designed to test the interaction between amyloid-β and tau proteins as a determinant of metabolic decline in preclinical Alzheimers disease (AD). We assessed 120 cognitively normal individuals with [|sup|18|/sup|F]florbetapir positron emission tomography (PET) and cerebrospinal fluid …
Authors: Morris, Martha Clare , Evans, Denis A. , Schneider, Julie A. , Tangney, Christine C. , Bienias, Julia L. , Aggarwal, Neelum T. Article Type: Research Article Abstract: Context: It is currently not known whether dietary intakes of folate and vitamins B12 and B6, co-factors in the methylation of homocysteine, protect against Alzheimers disease. Objective: To examine the association between risk of incident Alzheimers disease and dietary intakes of folate, vitamin B-12, and vitamin B-6. Design: Prospective cohort study. Setting: Geographically defined biracial Chicago community. Participants: 1,041 residents, aged 65 years and older, initially free of Alzheimers disease and followed a median 3.9 years for the development of incident disease. Main Outcome Measure: Probable Alzheimers disease identified through …structured clinical neurological evaluation using standardized criteria. Results: A total of 162 persons developed incident Alzheimers disease during follow-up. In logistic ...
TY - JOUR. T1 - Cystatin C - a novel genetic risk factor for late onset alzheimers disease. AU - Crawford, F.. AU - Freeman, M.. AU - Schinka, J.. AU - Morris, M.. AU - Abdullah, L.. AU - Duara, R.. AU - Mulla, M.. PY - 2000/8/7. Y1 - 2000/8/7. N2 - We investigated the occurrence of a Cystatin C genetic variant in 312 Caucasian clinic-based Alzheimers Disease (AD) cases versus 136 age-matched population-based Caucasian controls (age/age of onset range 60-91yrs). Logistic regression analyses revealed a significant 3-way interaction between APO-E e4 genotypes (APO-E4), CST3 G/G genotype and age/age of onset on AD diagnosis (p,.05) suggesting that the genetic risk changes differentially for APO-E or CST3 as a function of age. We stratified our sample based on age/age of onset of 80+yrs versus younger. In the younger group (231 cases; 86 controls) APOE4 conferred significant risk for AD (p,.0001) while CST3 genotype did not (p=.09). In the 80+ group (50 cases; 81 controls) APOE4 no longer ...
Dental health problems in Alzheimers patients can lead to pain, unmanageable behavior and extensive dental treatment. Yet, the dental needs of Alzheimers patients are often overlooked, usually for very understandable reasons: the patients forgetfulness results in unintentional dental neglect; medications may cause chronic "dry mouth" (reduction in the healthy flow of saliva) that can lead to tooth decay; patients and their families lose contact with their dentist because they are focused on other health issues.. Good dental health can make eating and digesting food easier for an Alzheimers patient, improving the overall quality of life. If you are a caregiver for someone suffering from Alzheimers, here are some tips and techniques from the Alzheimers Association to assist your loved one in maintaining good oral health.. ...
The cognitive profile of Alzheimer patients without (AD E-, n=17) and with (AD, E+, n=15) extrapyramidal signs (rigidity or bradykinesia), at the time of diagnosis, was examined in a 3-year follow-up
A study involving 159 older adults (average age 76) has confirmed that the amount of brain tissue in specific regions is a predictor of Alzheimers disease development. Of the 159 people, 19 were classified as at high risk on the basis of the smaller size of nine small regions previously shown to be vulnerable to Alzheimers), and 24 as low risk. The regions, in order of importance, are the medial temporal, inferior temporal, temporal pole, angular gyrus, superior parietal, superior frontal, inferior frontal cortex, supramarginal gyrus, precuneus.. There was no difference between the three risk groups at the beginning of the study on global cognitive measures (MMSE; Alzheimers Disease Assessment Scale-cognitive subscale; Clinical Dementia Rating-sum of boxes), or in episodic memory. The high-risk group did perform significantly more slowly on the Trail-making test part B, with similar trends on the Digit Symbol and Verbal Fluency tests.. After three years, 125 participants were re-tested. Nine ...
The Alzheimers Disease Research Center (ADRC) at the Icahn School of Medicine at Mount Sinai is a comprehensive research facility and clinical program dedicated to the study and treatment of normal aging and Alzheimers disease.
The identification of mutations in the APP, PS1, and PS2 genes that cause early-onset familial Alzheimers disease (AD), the demonstration that these mutations all increase Abeta42, and the discovery of an association between Apolipoprotein E4 and late-onset Alzheimers disease have dramatically improved our understanding of Alzheimers disease. It is clear, however, that much of the genetic risk in late onset Alzheimers disease remains unexplained. Current strategies to identify other genes that affect late-onset Alzheimers disease have met with limited success often because of the difficulty associated with obtaining late-onset families with sufficient power for reliable linkage analysis. Genetic studies using large numbers of small families or sib-pairs, to increase the power of the analysis, are also currently being performed by several groups however difficulties with the non-replication of positive loci, identified by different studies, has continued. It will also be difficult to ...
The first thing we must bear in mind is that Alzheimers disease isnt a normal part of aging. Thats how Alzheimers differs from Dementia. However, it is fair to say that Alzheimers disease is one of the most common forms of Dementia (70% of all cases). It causes global cognitive deterioration, behavioral disturbances and diffused cortical atrophy associated with neuronal degeneration. Although its prevalence is much higher in the senior population, it is also considered the most frequent form of dementia among those under-65. However, the 65 years mark is merely based on sociological aspects, and it has no biological significance in clinical practice.. What Alice faces is early-onset Alzheimers, a form of the disease that is far rarer than common Alzheimers disease, and often affects people in their prime, regardless of how mentally active they are. This is because early-onset Alzheimers is a genetically conditioned disease, with few environmental factors.. ...
The Alzheimers Disease Neuroimaging Initiative (ADNI) unites researchers with study data as they work to define the progression of Alzheimers disease. ADNI researchers collect, validate and utilize data such as MRI and PET images, genetics, cognitive tests, CSF and blood biomarkers as predictors for the disease. Data from the North American ADNIs study participants, including Alzheimers disease patients, mild cognitive impairment subjects and elderly controls, are available from this site.. ...
Calcium: A proven target in the war on Alzheimers disease Alzheimers disease is practically a household word these days, as the number of individuals dia
In this study, we have evaluated the levels of blood histamine, serum interleukin-1 beta (IL-1 beta), and plasma tumor necrosis factor-alpha (TNF-alpha) in 20 patients with mild to moderate Alzheimer disease (AD; 13 early onset and 7 late-onset AD subjects) and in 20 age-matched control subjects (C) …
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The UW Alzheimers Disease Research Center seeks to advance research in genetic risk, develop neuroimaging biomarkers for preclinical detection, and discover novel treatment strategies, in affiliation with the UW Memory and Brain Wellness Center.
The UW Alzheimers Disease Research Center seeks to advance research in genetic risk, develop neuroimaging biomarkers for preclinical detection, and discover novel treatment strategies, in affiliation with the UW Memory and Brain Wellness Center.
The overall goal of the proposed renewal of the Wisconsin Alzheimers Disease Research Center (Wisconsin ADRC) is to support cutting-edge and innovative researc...
Obstructive sleep apnea (OSA) is much more common in the elderly than in the young; the latest studies show prevalence between 45% and 62% in individuals over 60. It is even higher in patients with dementia such as Alzheimer patients.. Several trials in elderly patients showed modified cognitive functions, particularly executive and attentional functions, in patients with respiratory sleep disorder. However the benefit of CPAP (Continuous Positive Airway Pressure) ventilation for Alzheimer patients is still controversial, as there are few studies documenting its effects on dementia patients cognitive abilities, and clinicians appear reluctant to prescribe this type of treatment.. The investigators must keep in mind that Alzheimer patients suffer significant sleep disorders; advanced- stage patients spend 40% of the night awake and are drowsy a large part of the day. In dementia patients, sleep disorder is a major cause of hospitalization and institutionalization. The prevalence of obstructive ...
Obstructive sleep apnea (OSA) is much more common in the elderly than in the young; the latest studies show prevalence between 45% and 62% in individuals over 60. It is even higher in patients with dementia such as Alzheimer patients.. Several trials in elderly patients showed modified cognitive functions, particularly executive and attentional functions, in patients with respiratory sleep disorder. However the benefit of CPAP (Continuous Positive Airway Pressure) ventilation for Alzheimer patients is still controversial, as there are few studies documenting its effects on dementia patients cognitive abilities, and clinicians appear reluctant to prescribe this type of treatment.. The investigators must keep in mind that Alzheimer patients suffer significant sleep disorders; advanced- stage patients spend 40% of the night awake and are drowsy a large part of the day. In dementia patients, sleep disorder is a major cause of hospitalization and institutionalization. The prevalence of obstructive ...
A bit of peanut butter and a ruler may be an easy way confirm a diagnosis of early-stage Alzheimers disease, U.S. researchers say.
Brussels, Belgium, 19 July 2017 - Today, the Innovative Medicines Initiative (IMI) is launching two new Calls for proposals with topics on Alzheimers disease, big data, vaccines, autoimmune disease, the blood-brain barrier, drug development, and the exploitation of IMI project results. The total budget for the two Calls stands at just over EUR 130 million. Around half of this comes from the European Commissions Horizon 2020 programme. The other half comes from EFPIA companies as well as IMI Associated Partners.
The ε4 allele of apolipoprotein E (ApoE) accounts for an estimated 45-60% of the genetic risk for late onset sporadic Alzheimers disease, suggesting that it may be possible to identify other genetic loci that could account for the remaining risk associated with this disease. Recently, a biallelic polymorphism (G/A) in the 3′ untranslated region (UTR) of the transcription factor LBP-1c/CP2/LSF (for brevity, CP2) has been implicated in Alzheimers disease susceptibility, with the 3′-UTR A allele being associated with a reduction in the risk of sporadic Alzheimers disease.1-3 The CP2 gene is a plausible candidate for influencing Alzheimers disease risk: it is located near the LDL receptor related protein gene within the Alzheimers disease linkage region on chromosome 12; it controls the expression of several genes (α2 macroglobulin, glycogen synthase kinase-3β); and it interacts with different proteins (serum amyloid A3, interleukin 1α, tumour necrosis factor α, and Fe65 protein) and ...
TY - JOUR. T1 - Amyloid β peptide load is correlated with increased β-secretase activity in sporadic Alzheimers disease patients. AU - Li, Rena. AU - Lindholm, Kristina. AU - Yang, Li Bang. AU - Yue, Xu. AU - Citron, Martin. AU - Yan, Riqiang. AU - Beach, Thomas. AU - Sue, Lucia. AU - Sebbagh, Marwan. AU - Cai, Huaibin. AU - Wong, Philip. AU - Price, Donald. AU - Shen, Yong. PY - 2004/3/9. Y1 - 2004/3/9. N2 - Whether elevated β-secretase (BACE) activity is related to plaque formation or amyloid β peptide (Aβ) production in Alzheimers disease (AD) brains remains inconclusive. Here, we report that we used sandwich enzyme-linked immunoabsorbent assay to quantitate various Aβ species in the frontal cortex of AD brains homogenized in 70% formic acid. We found that most of the Aβ species detected in rapidly autopsied brains (,3 h) with sporadic AD were Aβ1-x and Aβ1-42, as well as Aβx-42. To establish a linkage between Aβ levels and BACE, we examined BACE protein, mRNA expression and ...
TY - JOUR. T1 - Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimers disease. AU - De Roeck, Arne. AU - Van den Bossche, Tobi. AU - van der Zee, Julie. AU - Verheijen, Jan. AU - De Coster, Wouter. AU - Van Dongen, Jasper. AU - Dillen, Lubina. AU - Baradaran-Heravi, Yalda. AU - Heeman, Bavo. AU - Sanchez-Valle, Raquel. AU - Lladó, Albert. AU - Nacmias, Benedetta. AU - Sorbi, Sandro. AU - Gelpi, Ellen. AU - Grau-Rivera, Oriol. AU - Gómez-Tortosa, Estrella. AU - Pastor, Pau. AU - Ortega-Cubero, Sara. AU - Pastor, Maria A. AU - Graff, Caroline. AU - Thonberg, Håkan. AU - Benussi, Luisa. AU - Ghidoni, Roberta. AU - Binetti, Giuliano. AU - de Mendonça, Alexandre. AU - Martins, Madalena. AU - Borroni, Barbara. AU - Padovani, Alessandro. AU - Almeida, Maria Rosário. AU - Santana, Isabel. AU - Diehl-Schmid, Janine. AU - Alexopoulos, Panagiotis. AU - Clarimon, Jordi. AU - Lleó, Alberto. AU - Fortea, Juan. AU - Tsolaki, Magda. AU - Koutroumani, Maria. AU - Matěj, ...
Eventbrite - Alzheimers Association, Hudson Valley Chapter presents Alzheimers Disease & Related Disorders Association, Inc. Hudson Valley Chapters 2015 Year End Appeal - Monday, December 7, 2015 | Monday, February 29, 2016 - Find event and ticket information.
Many patients currently diagnosed with very mild or mild Alzheimer disease dementia could potentially be reclassified as having mild cognitive impairment (MCI) under revised criteria for that condition, according to a report published Online First by Archives of Neurology, one of the JAMA/Archives journals.. The National Institute on Aging and the Alzheimers Association convened a work group to update criteria for MCI, and the revised criteria allow "considerable latitude" as to what represents functional independence, writes the studys sole author, John C. Morris, M.D., of Washington University School of Medicine in St. Louis. For example, "mild problems" performing daily activities such as shopping, paying bills and cooking are permissible, as is dependency on aids or assistance to complete those tasks.. In this study, the functional ratings of patients enrolled at federally funded Alzheimers Disease Centers with clinical and cognitive data maintained by the National Alzheimers ...
This new book presents a summary of Alzheimers disease-related ischemic protein changes and gene expression as risk factors for the late-onset of sporadic Alzheimers disease, and their role in Alzheimers disease ischemic etiology. Ischemic brain changes were noted in the staining of different parts of an amyloid protein precursor, presenilin 1 and 2, tau protein, alfa-synuclein, and apolipoproteins A1, E and J.. Current advances in understanding the ischemic etiology of Alzheimers disease has revealed dysregulation of Alzheimers disease-associated genes including presenilin 1 and 2, β-secretase, amyloid protein precursor, apoptosis, autophagy, mitophagy, and tau protein. This book presents the relationship between these genes, dysregulated by cerebral ischemia, and the cellular and tissue neuropathology characteristic of Alzheimers disease. This book draws attention to the latest research confirming the theory that Alzheimers disease-related proteins and genes play an important role in ...
The presence of Abeta(pE3) (N-terminal truncated Abeta starting with pyroglutamate) in Alzheimers disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of Abeta peptides in senile plaques of AD brains. This was later confirmed by other reports investigating AD and Downs syndrome postmortem brain tissue. Importantly, Abeta(pE3) has a higher aggregation propensity, and stability, and shows an increased toxicity compared to full-length Abeta. We have recently shown that intraneuronal accumulation of Abeta(pE3) peptides induces a severe neuron loss and an associated neurological phenotype in the TBA2 mouse model for AD. Given the increasing interest in Abeta(pE3), we have generated two novel monoclonal antibodies which were characterized as highly specific for Abeta(pE3) peptides and herein used to analyze plaque deposition in APP/PS1KI mice, an AD model with severe neuron loss and learning deficits. This was compared with the plaque ...
Alzheimers Disease is a progressive neurodegenerative illness characterized by short-term memory loss, disorientation, and impairments in socialization, self-care and behavioral regulation. It is primarily a disease of old age and affects over 5,000,000 Americans. Medications are often prescribed to manage its symptoms, but no medication has been shown to halt or delay the progression of the disease.. Given the enormous personal, social, and economic consequences of this illness, researchers are actively seeking novel ways to slow and forestall its devastating effects.. In a randomized clinical trial, Quintana-Hernández et al. [Journal of Alzheimers Disease] compared the effectiveness of a Mindfulness-Based Alzheimers Stimulation (MBAS) program in maintaining cognitive functioning in Alzheimers patients to that of two current non-pharmacological interventions for Alzheimers disease; namely, Progressive Muscle Relaxation (PMR) and Cognitive Stimulation Therapy (CST).. The researchers ...
Fagan, A. M., Mintun, M. A., Shah, A. R., Aldea, P., Roe, C. M., Mach, R. H., Marcus, D., Morris, J. C. and Holtzman, D. M. (2009), Cerebrospinal fluid tau and ptau181 increase with cortical amyloid deposition in cognitively normal individuals: Implications for future clinical trials of Alzheimers disease. EMBO Mol Med, 1: 371-380. doi: 10.1002/emmm.200900048 ...
BACKGROUND: Knowledge of the evolution of cognitive deficits in Alzheimer disease is important for our understanding of disease progression. Previous reports, however, have either lacked detail or have not covered the presymptomatic stages. OBJECTIVE: To delineate the onset and progression of clinical and neuropsychological abnormalities in familial Alzheimer disease. METHODS: Nineteen subjects with familial Alzheimer disease underwent serial clinical and neuropsychological assessments. Eight of these had undergone presymptomatic assessments. The follow-up period was 1 to 10 years (mean, 5 years). The relative timing of the occurrence of 3 markers of disease onset and progression (onset of symptoms, Mini-Mental State Examination score , or = 24, and impaired scores on a range of neuropsychological tests) were compared using the binomial exact test. RESULTS: Neurological abnormalities were not prominent, although myoclonus appeared early in some. Mini-Mental State Examination score was not ...
Title: Serum Amyloid Beta Peptides in Patients with Dementia and Age-Matched Non-Demented Controls as Detected by Surface-Enhanced Laser Desorption Ionisation-Time of Flight Mass Spectrometry (SELDI-TOF MS). VOLUME: 3 ISSUE: 3. Author(s):Suzanne V. Frankfort, Jos P.C.M. van Campen, Linda R. Tulner and Jos H. Beijnen. Affiliation:Department of Pharmacy&Pharmacology, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands.. Keywords:Serum Amyloid Beta Peptides, dementia, SELDI-TOF MS, Alzheimers Disease, CSF profile, diagnosis, DNA Isolation, Genotype Analysis. Abstract: Background: By using surface enhanced laser desorption/ionisation- time of flight mass spectrometry (SELDITOF MS) an amyloid ß (Aß) profile was shown in cerebrospinal fluid (CSF) of patients with dementia. Objective: To investigate the Aβ-profile in serum with SELDI-TOF MS, to evaluate if this profile resembles CSF profiles and to investigate the correlation between intensity of Aβ-peptide-peaks in serum and ...
- Treatment with Nypta(R) (Tideglusib) (NP-12) was tolerated and produced positive effects on Alzheimers patients in four of the five efficacy variables examined in the trial.
The uridine nucleotide-activated P2Y2, P2Y4 and P2Y6 receptors are widely expressed in the brain and are involved in many CNS processes, including those which malfunction in Alzheimers disease (AD). However, the status of these receptors in the AD neocortex, as well as their putative roles in the pathogenesis of neuritic plaques and neurofibrillary tangles, remain unclear. In this study, we used immunoblotting to measure P2Y2, P2Y4 and P2Y6 receptors in two regions of the postmortem neocortex of neuropathologically assessed AD patients and aged controls. P2Y2 immunoreactivity was found to be selectively reduced in the AD parietal cortex, while P2Y4 and P2Y6 levels were unchanged. In contrast, all three receptors were preserved in the occipital cortex, which is known to be minimally affected by AD neuropathology. Furthermore, reductions in parietal P2Y2 immunoreactivity correlated both with neuropathologic scores and markers of synapse loss. These results provide a basis for considering P2Y2 receptor
Most people with Alzheimers disease have the late-onset form of the disease, in which symptoms become apparent in their mid-60s.The apolipoprotein E (APOE) gene is involved in late-onset Alzheimers. This gene has several forms. One of them, APOE ε4, increases a persons risk of developing the disease and is also associated with an earlier age of disease onset. However, carrying the APOE ε4 form of the gene does not mean that a person will definitely develop Alzheimers disease, and people with no APOE ε4 may also develop the disease.. Also, scientists have identified a number of regions of interest in the genome (an organisms complete set of DNA) that may increase a persons risk for late-onset Alzheimers to varying degrees.. Early-onset Alzheimers disease occurs in people age 30 to 60 and represents less than 5 percent of all people with Alzheimers. Most cases are caused by an inherited change in one of three genes, resulting in a type known as early-onset familial Alzheimers disease, ...
The Pentacam HR Scheimpflug imaging was performed on 10 eyes from 10 Alzheimers disease patients and 10 eyes of 10 age and sex matched control patients (Figure). The average age of Alzheimers disease patients was 72.3±9.9 years and that of control patients was 68.3±6.78 years. The average and maximum densities of the supranuclear lens region were consistently higher in Alzheimers disease patients (12.28±1.25 and 24.72±6.01, respectively), when compared to age and sex matched controls (11.82±1.67 and 22.40±4.3). However, there was no statistically significant difference in these variables between the two groups (p=0.33 and p=0.50).. ...
Dr. Richard Mayeux is the Gertrude H. Sergievsky Professor of Neurology, Psychiatry and Epidemiology, chair of the Department of Neurology at Columbia University College of Physicians and Surgeons, and Neurologist-in-Chief at NewYork-Presbyterian/Columbia University Medical Center. Dr. Mayeux is also director of the Gertrude H. Sergievsky Center, a center devoted to the epidemiologic investigation of neurological diseases, and co-director of the Taub Institute for Research on Alzheimers Disease and the Aging Brain at Columbia University Medical Center.. Dr. Mayeux graduated with distinction from the University of Oklahoma School of Health Sciences and trained in Internal Medicine at the Boston City Hospital and in Neurology at the Columbia Presbyterian Medical Center in New York. He completed a fellowship in the study of disorders of behavior, language, and cognition with the late D.Frank Benson in Boston. Dr. Mayeux completed graduate work in epidemiology at the Columbia University Mailman ...
The progression and symptoms of early-onset Alzheimers Disease, typically identified in patients in their 40s or 50s, can vary dramatically depending on the individual. According to the Alzheimers Association,
The study involved 20 subjects with Alzheimers disease or mild cognitive impairment who, on separate days, were given either emulsified MCTs or a placebo. The researchers observed a significant increase in blood plasma levels of the ketone body beta-hydroxylutyrate (beta-OHB) after only 90 minutes of treatment, and depending on the apolipoprotein E genotype of the subject tested, beta-OHB levels either continued to rise or held constant between the 90 and 120 minute blood draws in the treatment condition. Remarkably, cognitive testing revealed that this brief MCT treatment facilitated improved performance on the Alzheimers Disease Assessment Scale-Cognitive Subscale (ADAS-cog) in 4 subjects within the study group. Moreover, "higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to placebo across all subjects (P=0.02)."[i ...
On October 4, the Alzheimer Society of B.C., Brain Canada, Genome British Columbia, the Michael Smith Foundation for Health Research and the Pacific Alzheimer Research Foundation will have an in-depth discussion of how research is moving towards a cure for Alzheimers disease and other dementias. An expert panel will break down the current state of dementia research, including the crucial role played by individuals and families living with the disease. Afterwards, a Q&A session will open the floor for public discussion.. If you or someone in your life is living with the disease, or if youre interested in how B.C. researchers are confronting it, dont miss out. Registration is free, but spaces are limited.. Event details: ...
The CLU gene is located on p21-p12 of human chromosome 8, with CLU as its encoded product, which has various physiological functions, including participating in lipid metabolism (28), oxidative stress reaction (29), and cell cycle regulation (30). CLU is highly expressed in cerebrospinal fluid and amyloid plaques in brain tissues, and is involved in the pathogenesis of AD (4,5,31). Yerbury et al (32) demonstrated that the deposition of CLU in senile plaques and neurofibrillary tangles of AD. Howlett et al (33) further reported a correlation between CLU and senile plaque Aβ40 in the brain cortex of patients with AD. Martin-Rehrmann et al (34) demonstrated the presence of dysfunctional neurons with phosphorylated tau protein surrounding the senile plaques in 71% of CLU-positive patients with AD. Furthermore, they also showed that the tau and phosphorylated tau protein were significantly increased in the rat hippocampus, following the injection of a CLU-rich solution (34). It was suggested that ...
The new potential treatment offers a different approach from the traditional tactic of targeting the amyloid plaques and tangles that develop in the brains of Alzheimers patients. Until recently, most researchers believed these plaques and tangles caused the cognitive decline. But the failure of this hypothesis to lead to an effective treatment for Alzheimers disease has caused some scientists to theorize that, though the plaques and tangles are always associated with the disease, they may not be the main cause of the dementia, nor the best target for treating it ...
Authors: Tan, Meng-Shan , Yang, Yu-Xiang , Wang, Hui-Fu , Xu, Wei , Tan, Chen-Chen , Zuo, Chuan-Tao , Dong, Qiang , Tan, Lan , Yu, Jin-Tai , Alzheimers Disease Neuroimaging Initiative Article Type: Research Article Abstract: Background: Amyloid-β (Aβ) plaques and tau neurofibrillary tangles are two neuropathological hallmarks of Alzheimers disease (AD), which both can be visualized in vivo using PET radiotracers, opening new opportunities to study disease mechanisms. Objective: Our study investigated 11 non-PET factors in 5 categories (including demographic, clinical, genetic, MRI, and cerebrospinal fluid (CSF) features) possibly affecting PET amyloid and tau status to explore the relationships between amyloid and tau pathology, and whether these features had a different association with amyloid and tau status. Methods: We included 372 nondemented elderly from the Alzheimers Disease Neuroimaging Initiative cohort. …All underwent PET amyloid and tau analysis simultaneously, and were ...
Alzheimer's disease,[71] Huntington's disease,[72] Rett syndrome,[73] and dementia,[74] as well as anorexia nervosa[75] and ... "BDNF and Alzheimer's Disease - What's the Connection?". Alzforum: Live Discussions. Alzheimer Research Forum. Archived from the ... Alzheimer's disease[edit]. Post mortem analysis has shown lowered levels of BDNF in the brain tissues of people with ... "New insights into brain BDNF function in normal aging and Alzheimer disease". Brain Research Reviews. 59 (1): 201-20. doi: ...
"Genetic determinants of disease progression in Alzheimer's disease". Journal of Alzheimer's Disease. 43 (2): 649-55. doi: ... Table 1. CASS4 disease association Screen purpose Observation Alzheimer's disease SNP rs7274581 T/C linked to risk.. Odds ratio ... "Alzheimer's disease risk genes and mechanisms of disease pathogenesis". Biological Psychiatry. 77 (1): 43-51. doi:10.1016/j. ... Alzheimer's disease[edit]. CASS4 and corresponding SNP - rs7274581 T/C has been identified in a large meta-analysis as a locus ...
Alzheimer's disease[edit]. In 2000 and 2001, Merck conducted several studies of rofecoxib aimed at determining if the drug ... Fitzgerald GA (October 2004). "Coxibs and cardiovascular disease". The New England Journal of Medicine. 351 (17): 1709-11. doi: ... The plaintiff, a 71-year-old smoker with heart disease, had a fatal heart attack three weeks after finishing a one-week sample ... slowed the onset of Alzheimer's disease. Merck has placed great emphasis on these studies on the grounds that they are ...
Alzheimer's Disease International.. *^ a b Beach, T.G.; et al. (2012). "Accuracy of the Clinical Diagnosis of Alzheimer Disease ... 2015). "Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer disease: Phase 3 study". Alzheimer's & Dementia. 11 ... Alzheimer's disease and amyloid-beta PET imaging[edit]. More than 44 million people worldwide have been diagnosed with some ... "The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's ...
Alzheimer's disease. HSV-1 has been proposed as a possible cause of Alzheimer's disease.[26][27] In the presence of a certain ... Itzhaki RF, Wozniak MA (May 2008). "Herpes simplex virus type 1 in Alzheimer's disease: the enemy within". J. Alzheimers Dis. ... Dobson CB, Itzhaki RF (1999). "Herpes simplex virus type 1 and Alzheimer's disease". Neurobiol. Aging. 20 (4): 457-65. doi: ... HSV infection has also been associated with cognitive deficits of bipolar disorder,[13] and Alzheimer's disease, although this ...
Alzheimer's disease[edit]. The PCC is commonly affected by neurodegenerative disease.[15] In fact, reduced metabolism in the ... in Alzheimer's .[4] In Alzheimer's disease, the topology of white matter connectivity helps in predicting atrophic patterns,[17 ... 1999) show that experimental damage of the rhinal cortex results in hypometabolism of the PCC.[16] In Alzheimer's disease, ... Alzheimer's Disease).[6] The posterior cingulate cortex has also been firmly linked to emotional salience.[6][7] Thus, it has ...
... has been linked to Alzheimer's disease as well as other metabolic and vascular diseases.[3] ... Alzheimer's disease[edit]. Based on studies, it is evident that obesity has a strong association with vascular and metabolic ... Razay, G.; Vreugdenhil, A.; Wilcock, G. (2006). "Obesity, abdominal obesity and Alzheimer disease". Dementia and Geriatric ... disease which could potentially be linked to Alzheimer's disease. Recent studies have also shown an association between mid- ...
Alzheimer disease with concomitant dementia with Lewy bodies (AD+DLB)[edit]. The degree of NFT involvement in AD is defined by ... 3.4 Alzheimer disease with concomitant dementia with Lewy bodies (AD+DLB). *3.5 Link to aggression and depression in ... Journal of Alzheimer's Disease. 19 (2): 705-719. doi:10.3233/JAD-2010-1276. PMID 20110614.. ... 2005). "Tau phosphorylation in Alzheimer's disease: pathogen or protector?". Trends in Molecular Medicine. 11 (4): 164-169. doi ...
Alzheimer's disease[edit]. Studies on arachidonic acid and the pathogenesis of Alzheimer's disease is mixed, with one study of ... In adults, the disturbed metabolism of ARA may contribute to neuropsychiatric disorders such as Alzheimer's disease and bipolar ... "Detrimental effects of arachidonic acid and its metabolites in cellular and mouse models of Alzheimer's disease: Structural ... "Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease". ...
Alzheimer's disease[edit]. Claims have been made of a sugar-Alzheimer's disease connection, but there is inconclusive evidence ... Excessive consumption of sugar has been implicated in the onset of obesity, diabetes, cardiovascular disease, dementia, and ... while promoting saturated fat as the main dietary risk factor in cardiovascular diseases.[88] In 2016, the criticism led to ... to cure cold diseases, and sooth lung complaints".[24] ... non-communicable disease] policy".[95] There have been similar ...
... may help slow or stop Alzheimer's disease[12]. For Alzheimer's disease[edit]. Several companies are in the early stages of ... relevance in Alzheimer's disease". Neuro-Degenerative Diseases. 4 (2-3): 117-26. doi:10.1159/000101836. PMID 17596706.. ... two unusual aspartyl proteases involved in Alzheimer's disease". Neuro-Degenerative Diseases. 1 (4-5): 168-74. doi:10.1159/ ... "Merck Initiates Phase II/III Study of Investigational BACE Inhibitor, MK-8931, for Treatment of Alzheimer's Disease". December ...
Discoveries concerning pathogenic mechanisms in Alzheimer's disease and other diseases. Awards. Denham Harman Research Award, ... "JOURNAL OF ALZHEIMER'S DISEASE. Retrieved 2018-05-14.. *^ "Archived copy". Archived from the original on 2009-09-12. Retrieved ... underlying selective neuronal death in neurodegenerative diseases such as Alzheimer's disease. Further this research involves a ... Smith served as Editor-in Chief of Journal of Alzheimer's Disease and also sat on the Editorial Board of over 20 leading ...
Alzheimer disease Decrease in right medial temporal cortex 10+10 [17] Radioligands[edit]. Labeled with the radioisotope carbon- ... "A positron emission tomography study of 5-hydroxytryptamine-1A receptors in Alzheimer disease". American Journal of Geriatric ... Disease. Result. Subjects. Ref. Depressive (with primary, recurrent, familial mood disorders) Reduction in raphe nucleus and ...
Alzheimer's disease. 1,050. 2012[83]. −2%. Exforge (amlodipine/valsartan). Hypertension. 1,352. 2012[83]. 12%. ... Parkinson's disease. Tasigna (nilotinib). Chronic myelogenous leukemia (first-line treatment[89]). 998. 2012[83]. 39%. NICE ... 28 April 2011 Cheaper Drug to Treat Eye Disease Is Effective *^ a b Jeffreys, Branwen (2012-05-06). "Using Avastin for eye ... Copley, Caroline; Hirschler, Ben (24 April 2012), Potter, Mark, ed., Novartis challenges UK Avastin use in eye disease, Reuters ...
"Journal of Alzheimer's Disease. 14 (2): 133-45. doi:10.3233/JAD-2008-14202. PMC 2670571. PMID 18560126.. ... Alzheimer's Disease: A study published in Archives of Neurology in February 2003 suggested that the intake of both trans fats ... February 2003). "Dietary fats and the risk of incident Alzheimer disease". Archives of Neurology. 60 (2): 194-200. doi:10.1001/ ... report Prevention of cardiovascular disease declared that 40,000 cardiovascular disease deaths in 2006 were "mostly preventable ...
"Journal of Alzheimer's Disease. 14 (2): 133-145. doi:10.3233/JAD-2008-14202. PMC 2670571. PMID 18560126.. ... Alzheimer's Disease: A study published in Archives of Neurology in February 2003 suggested that the intake of both trans fats ... "Dietary fats and the risk of incident Alzheimer disease". Arch Neurol. 60 (2): 194-200. doi:10.1001/archneur.60.2.194. PMID ... report Prevention of cardiovascular disease declared that 40,000 cardiovascular disease deaths in 2006 were "mostly preventable ...
Journal of Alzheimer's Disease. 23 (4): 727-35. doi:10.3233/JAD-2011-101572. PMID 21304183.. ... Louis ED (2014). "'Essential tremor' or 'the essential tremors': is this one disease or a family of diseases?". ... cerebrovascular disease, abnormal bleeding, hemorrhage and/or blood clotting disorders, advanced kidney disease or on dialysis ... "Journal of Parkinson's Disease. 7 (2): 369-376. doi:10.3233/JPD-160992. ISSN 1877-7171.. ...
2013). "Treatment of Alzheimer's disease with the GSK-3 inhibitor tideglusib: A pilot study". Journal of Alzheimer's disease. ... Teodoro Del Ser (2010). "Phase IIa clinical trial on Alzheimer's disease with NP12, a GSK3 inhibitor". Alzheimer's & Dementia. ... Alzheimer's disease and progressive supranuclear palsy. As of 2017 it was undergoing Phase IIa[2] and IIb clinical trials.[3][4 ...
"Journal of Alzheimer's Disease. 29 (3): 561-9. doi:10.3233/JAD-2011-111751. PMID 22330823.. ... placebo-controlled trials published in the Journal of Alzheimer's Disease found that a daily multivitamin may improve immediate ... do not have a lower chance of diseases, such as cancer, heart disease, or diabetes. Based on current research, it's not ... Zhao LQ, Li LM, Zhu H, The Epidemiological Evidence-Based Eye Disease Study Research Group EY (February 2014). "The effect of ...
"Journal of Alzheimer's Disease. 64 (2): 367-378. doi:10.3233/jad-180160. PMID 29945352.. CS1 maint: Multiple names: authors ... In June 2018, Howard and Nolan were co-authors of a paper in the Journal of Alzheimer's Disease that reported the results of a ... Journal of Alzheimer's Disease. 61 (3): 947-961. doi:10.3233/JAD-170713. PMID 29332050.. CS1 maint: Multiple names: authors ... "Nutritional Intervention to Prevent Alzheimer's Disease: Potential Benefits of Xanthophyll Carotenoids and Omega-3 Fatty Acids ...
"Art therapy for Alzheimer's disease and other dementias". Journal of Alzheimer's Disease. 39 (1): 1-11. doi:10.3233/JAD-131295 ... "Efficacy of Creative Arts Therapy in Treatment of Alzheimer's Disease and Dementia: A Systematic Literature Review". Activities ... Art therapists work with populations of all ages and with a wide variety of disorders and diseases. Art therapists provide ... Art and the creative process can aid many illnesses (cancer, heart disease, influenza, etc.). People can escape the emotional ...
"Light Therapy and Alzheimer's Disease and Related Dementia: Past, Present, and Future". Journal of Alzheimer's Disease. 33 (4 ... Sleep Disorder in Alzheimer's Disease[edit]. Studies have shown that daytime and evening light therapy for nursing home ... "Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer's disease". American Journal of ... "Increased Light Exposure Consolidates Sleep and Strengthens Circadian Rhythms in Severe Alzheimer's Disease Patients". ...
Alzheimer's Disease Neuroimaging Initiative (2013). "How early can we predict Alzheimer's disease using computational anatomy ... sciences and computational modeling to quantitatively define and investigate problems in neurological and psychiatric diseases ...
Oxidative stress is thought to contribute to the development of a wide range of diseases including Alzheimer's disease,[159][ ... "Journal of Alzheimer's Disease. 29 (4): 711-26. doi:10.3233/JAD-2012-111853. PMC 3727637 . PMID 22366772.. ... "Biochemical and therapeutic effects of antioxidants in the treatment of Alzheimer's disease, Parkinson's disease, and ... Although dietary antioxidants have been investigated for potential effects on neurodegenerative diseases such as Alzheimer's ...
Russo P, Frustaci A, Del Bufalo A, Fini M, Cesario A (2013). "Multitarget drugs of plants origin acting on Alzheimer's disease ... used to treat Alzheimer's disease. Other plant-derived drugs, used medicinally and/or recreationally include morphine, cocaine ... Natural products sometimes have therapeutic benefit as traditional medicines for treating diseases, yielding knowledge to ... as a drug to alleviate disease). Drugs such as penicillin, morphine, and paclitaxel proved to be affordably acquired at needed ...
A comparison of beta-amyloid deposition in the medial temporal lobe in sporadic Alzheimer's disease, Down's syndrome and normal ... 大多數的基因是存在細胞核中,但是細胞中一個稱為粒線體的胞器,也擁有自己的基因組。粒線體基因組在粒線體疾病(mitochondrial disease)中具有一定的重要性。而且這些基因也可以用來研究人
Alzheimers disease is a brain disease and the most common form of a group of brain diseases called dementias, accounting for ... What is Alzheimers Disease?. Alzheimers disease is the most common form of a group of brain diseases called dementias. ... Nearly 6 million Americans are living with Alzheimers disease. Alzheimers disease destroys brain cells causing problems with ... What is known about caregiving for a person with Alzheimers disease or another form of dementia?. People with Alzheimers ...
... an interactive diagram of beta-amyloid formation and how they contribute to the development of plaques in the Alzheimers brain ... Alzheimers Disease and the Brain. 8 9 10 11 12 13 14 15 16 ... Alzheimers Association is a not-for-profit 501(c)(3) ... Stay up-to-date on advances in Alzheimers treatments, care & research. Get tips for living with Alzheimers. ... Alzheimers Association National Office, 225 N. Michigan Ave., Fl. 17, Chicago, IL 60601. ...
Tips and resources that can help with the challenges Alzheimers Caregivers face. ... Deaths from Alzheimers disease in the United States. Alzheimers disease is ultimately a fatal form of dementia. It is the ... Who has Alzheimers disease?. Scientists do not yet fully understand what causes Alzheimers disease. There probably is not one ... Alzheimers Association. 2016 Alzheimers disease facts and figures. Alzheimers Dement 2016; 12(4):459-509. ...
The disease is characterized by abnormal accumulation of plaques and by ... degenerative disease of nerve cells in the cerebral cortex that leads to atrophy of the brain and senile dementia and, ... Alzheimers disease. Alzheimers disease ăls´hī˝mərz, ôls- [key], degenerative disease of nerve cells in the cerebral cortex ... the disease is almost as significant as heart disease and cancer. The cause of Alzheimers is unknown, but a number of genes ...
Alzheimers disease is the most common cause of dementia. Dementia is a group of symptoms associated with a decline in the way ... Read more about the causes of Alzheimers disease.. Signs and symptoms of Alzheimers disease. Alzheimers disease is a ... Read more about diagnosing Alzheimers disease.. How Alzheimers disease is treated. Theres currently no cure for Alzheimers ... Can Alzheimers disease be prevented?. As the exact cause of Alzheimers disease is not clear, theres no known way to prevent ...
Familial Alzheimers disease[edit]. Familial Alzheimers disease (FAD) or early-onset familial Alzheimers disease (EOFAD) is ... Early-onset Alzheimers disease, also called early-onset Alzheimers, or early-onset AD, is Alzheimers disease diagnosed ... History of Alzheimers disease[edit]. Main article: Alzheimers disease § History. The symptoms of the disease as a distinct ... "Familial Alzheimers disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimers disease ...
Familial Alzheimers disease[edit]. Familial Alzheimers disease (FAD) or early onset familial Alzheimers disease (EOFAD) is ... Early-onset Alzheimers disease, also called early-onset Alzheimers, or early-onset AD, is Alzheimers disease diagnosed ... History of Alzheimers disease[edit]. Main article: Alzheimers disease § History. The symptoms of the disease as a distinct ... of all Alzheimers cases. Approximately 13% of the cases of early-onset Alzheimers are familial Alzheimers disease,[1] where ...
Alzheimers treatment and Alzheimers care go hand in hand. Theres no cure -- yet. But as youll see here, theres a lot that ... Living with Alzheimers disease means caring for the patient -- and caring for the caregiver. Heres how to manage both of ...
The UW Alzheimers Disease Research Center seeks to advance research in genetic risk, develop neuroimaging biomarkers for ... Alzheimers Disease Research Center - University of Washington An NIH-funded research resource center, associated with the UW ... Martin, the founder of the UW Alzheimers Disease Research Center. At age 90, he still studies the mechanisms of brain aging ... One mans creative quest to support Alzheimers disease research invites us to take a twirl through the science of brain ...
Alzheimer disease is a degenerative disease of the brain that causes dementia, which is a gradual loss of memory, judgment, and ... This type of Alzheimer disease is not inherited.. The causes of late-onset Alzheimer disease are less clear. The late-onset ... Alzheimer disease currently affects more than 5 million Americans. Because the risk of developing Alzheimer disease increases ... medlineplus.gov/genetics/condition/alzheimer-disease/ Alzheimer disease. ...
Alzheimers Disease. ​​Alzheimers disease is a type of dementia that causes problems with memory, thinking and behavior. ... Alzheimers disease accounts for 60 to 80 percent of dementia cases. Currently there is no cure for Alzheimers, but treatments ... Center for Chronic Disease Prevention and Health PromotionCurrently selected *Division of Chronic Disease and Injury Control * ... Although current Alzheimers treatments cannot stop the disease from progressing, they can temporarily slow the worsening of ...
Researchers discover novel genes responsible for Alzheimers disease. *Lithium in drinking water can slow Alzheimers disease ... There is no cure for Alzheimers disease, but several medications may improve certain symptoms as well as slowing disease ... Alzheimers disease is the most common form of dementia and affects millions of individuals worldwide. Dementia is a medical ... The exact cause of Alzheimers disease is not known, but a number of factors are thought to increase the risk of developing the ...
Alzheimers disease is a progressive form of dementia that interferes with memory, thinking, and behavior. Learn how to ... Symptoms of Alzheimers disease. Everyone has episodes of forgetfulness from time to time. But people with Alzheimers disease ... Diagnosing Alzheimers disease. The only definitive way to diagnose someone with Alzheimers disease is to examine their brain ... Treating Alzheimers disease. Theres no known cure for Alzheimers disease. But your doctor can recommend medications and ...
Two genome-wide association studies together report three new susceptibility loci for late-onset Alzheimers disease. CLU, ... Alzheimers disease susceptibility genes modify the risk of Parkinson disease and Parkinsons disease-associated cognitive ... Down syndrome, Alzheimer disease, and cerebral amyloid angiopathy: The complex triangle of brain amyloidosis *María Carmona‐ ... Translating Alzheimers disease-associated polymorphisms into functional candidates: a survey of IGAP genes and SNPs *Yuriko ...
Phelps talked about a report that found over 35 million people around the world are suffering from Alzheimers disease or other ... He discussed available treatment for patients and into the often undiagnosed disease, and he responded to telephone calls and ... New Report on Alzheimers Disease. Harry Johns talked about the release of the 2009 Alzheimers Disease Facts and Figures. The ... See all on Diseases * March 25, 2009. National Alzheimers Strategic Plan. The Alzheimers Study Group (ASG) released their ...
Alzheimer disease, degenerative brain disorder that develops in mid-to-late adulthood. It results in a progressive and ... Alzheimer diseaseOverview of Alzheimer disease.. Contunico © ZDF Enterprises GmbH, Mainz. The disease was first described in ... human disease: Alzheimers disease. …definitive diagnosis can be made. Alzheimers disease is the most common form of dementia ... nervous system disease: Dementia. …common cause of dementia is Alzheimer disease. The disease is common in the elderly. The ...
Learn about Alzheimers disease, dementia and memory loss symptoms, causes and risk factors and understand their relation to ... Learn more: Early Onset Alzheimers and Risk Factors *Alzheimers worsens over time. Alzheimers is a progressive disease, ... There is a lot to know about living with Alzheimers disease. Stay up-to-date on the latest advances in Alzheimers, plus get ... Learn more: 10 Warning Signs and Stages of Alzheimers Disease. *Alzheimers has no current cure, but treatments for symptoms ...
Alzheimers Disease *Alzheimers Disease Fact Sheet * Alzheimers Disease - NINDS *The Alzheimers Association information on ... Alzheimers Disease. What is Alzheimers Disease? In 1986, President Ronald Reagans "I dont remember," "I dont recall" ... are used to treat mild to moderate Alzheimers disease and memantine (Namenda), is used to treat moderate to severe Alzheimers ... Alzheimers disease ranks fourth in the cause of death among adults. About 100,000 people die per year as a result of AD. Five ...
With Democrat Ned Lamont poised to take over in January as Connecticuts next governor, Annie Lamont, as she is known, will step into a more public role as the states first lady.. ...
Read CNNs Fast Facts on Alzheimers disease, a progressive brain disorder that leads to loss of memory and other intellectual ... Alzheimers disease is fatal and there is no cure. It is a slow-moving disease that starts with memory loss and ends with ... Early-onset Alzheimers Disease:. Early-onset Alzheimers is an uncommon form of dementia that strikes people younger than age ... Early-onset Alzheimers disease often runs in families.. Research:. March 9, 2014 - In a first-of-its-kind study, researchers ...
The Alzheimers Association predicts that 720,000 Floridians will be diagnosed with the disease by 2025, a 44 percent increase ... A missing 80-year-old man with Alzheimers disease was found Sunday night, deputies say ... For those with Alzheimers, the holiday season is sometimes peppered with distress, experts say, but there are ways to keep it ... which will benefit Alzheimers Association of Central Florida. ... Alzheimers Disease Arts, aging experts seek to help caregivers ...
This presentation is an overview of Journal of Alzheimers Disease and the impact it has on the Alzheimers Disease research ... Journal of Alzheimers Disease, 2015 * 1. Journal of Alzheimers Disease 2015 Editorial Board Meeting Alzheimers Association ... This presentation is an overview of Journal of Alzheimers Disease and the impact it has on the Alzheimers Disease research ... Book Series: Advances in Alzheimers Disease  Vol. 1. Handbook of Animal models in Alzheimers Disease G. Casadesus (Ed.), ...
Alzheimers disease symptoms develop gradually and become more severe over time.In many people, symptoms can take as long as ... The exact cause of Alzheimers disease is not clearly understood, but patients with the condition have been found to have ... As a progressive condition, Alzheimers disease symptoms develop gradually and become more severe over time.In many people, ... Alzheimers Disease Symptoms. News-Medical. 24 October 2020. ,https://www.news-medical.net/health/Alzheimers-Disease-Symptoms. ...
Beliefnet offers spiritual resources to help bolster your strength as an Alzheimers Disease caregiver, as well as insights on ... Can You Prevent Alzheimers Disease?. Alzheimers disease is the most common form of dementia affecting people of the ages 65 ... 9 Signs of Alzheimers You Shouldnt.... If you suspect you or a loved one may have Alzheimers disease, here are some red ... Gift Ideas for People with Alzheimers.... The Alzheimers Association and the Alzheimer Foundation of America provide several ...
Alzheimers Disease is a progressive neurodegenerative disorder of late life with devastating consequences for the afflicted ... Alzheimers disease Alzheimer´s disease CNS Disease related genes Krankheitsbezogene Gene Therapeut Therapie biology cytokine ... Alzheimers Disease is a progressive neurodegenerative disorder of late life with devastating consequences for the afflicted ... Tau Phosphorylation and Dephosphorylation in the Pathogenesis of Alzheimers Disease M. Mawal-Dewan, J. Q. Trojanowski, V. M.-Y ...
  • As the disease progresses, the patient exhibits more serious problems, becoming subject to mood swings and unable to perform complex activities such as driving. (wikipedia.org)
  • As the disorder progresses, some people with Alzheimer disease experience personality and behavioral changes and have trouble interacting in a socially appropriate manner. (medlineplus.gov)
  • As Alzheimer's disease gradually progresses, people have increased difficulty performing their routine tasks at home, work, or in a social settings. (emoryhealthcare.org)
  • As a result, unwarranted emotional outbursts (referred to as catastrophic reactions), disturbing behaviors (such as wandering) and episodes of extreme agitation occur and become more frequent as the disease progresses. (healthcentral.com)
  • Alzheimer's disease is characterized by a gradual decline that generally progresses through three stages: early, middle and late stage disease. (ndss.org)
  • As the disease progresses, it is expected that abilities and skills decrease and the need for support and supervision increases, so aim to prepare proactively for each step. (ndss.org)
  • WASHINGTON (Sept. 11, 2015) -- The largest nationwide clinical trial to study high-dose resveratrol long-term in people with mild to moderate Alzheimer's disease found that a biomarker that declines when the disease progresses was stabilized in people who took the purified form of resveratrol. (eurekalert.org)
  • Because the risk of developing Alzheimer disease increases with age and more people are living longer, the number of people with this disease is expected to increase significantly in coming decades. (medlineplus.gov)
  • Some evidence indicates that people with Down syndrome have an increased risk of developing Alzheimer disease. (medlineplus.gov)
  • Today, we know that about 5.1 million Americans suffer from Alzheimer's disease, and health officials estimate that the aging of the U.S. population may result in 3 times as many cases by 2050. (nih.gov)
  • However, individuals who suffer from Alzheimer's disease may forget things more often, but they do not remember them again. (bartleby.com)
  • In the US around four million men and women suffer from Alzheimer's disease (AD), and in the UK over 600,000, mostly over the age of 65 years. (healthy.net)
  • The Alliance for Aging Research and a coalition of non-profit organizations it chairs known as ACT-AD, for Accelerate Cure/Treatments for Alzheimer's Disease, is at the forefront of efforts to advance the development of transformational therapies for Alzheimer's disease. (prnewswire.com)
  • Although the findings are encouraging, the scientists caution that it would be premature for people to take antidepressants solely to slow the development of Alzheimer's disease. (newswise.com)
  • You're going to have to move early and be very aggressive," said Reisa Sperling, who directs the Center for Alzheimer Research and Treatment at Brigham and Women's Hospital in Boston. (usatoday.com)