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 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, 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.

*  The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice | SpringerLink

Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early Stage Disease; Availability. [ ... Despite years of research, there are no disease-modifying drugs for Alzheimer's disease (AD), a fatal, age-related ... Goedert M, Spillantini MG: A century of Alzheimer's disease. Science. 2006, 314: 777-781. 10.1126/science.1132814.PubMedGoogle ... Wollen KA: Alzheimer's disease: the pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a ...

*  Pet Store Fish Provide Clue to How Alzheimer's Disease May Start

report that studies with zebrafish have provided an important clue to understanding how Alzheimer's disease begins. ... Alzheimer's Disease. Streetwise Reports Examines How Possible 'Best-in-Class' Alzheimer's Drug Candidate Offers 'Disruptive' ... "There is a major shift in the field toward Alzheimer's disease prevention, with a push for early biomarkers to identify ... Pet Store Fish Provide Clue to How Alzheimer's Disease May Start Comments ...

*  Alzheimer's & Dementia Weekly: "Alzheimer's-in-a-Dish" Docs Win Top Smithsonian Ingenuity Award

ABOVE: In Tanzi and Kim's lab, brain cells growing in 3-D in a dish harbor genes for familial Alzheimer's disease. Each of ... Yet Alzheimer's patients can't do without care: The disease progresses from the early stages of chronic forgetfulness, ... On learning that people with Down often end up contracting Alzheimer's disease as well, Tanzi realized he had found his life's ... An estimated five million Americans are stricken with Alzheimer's disease, and that figure is expected to quadruple in the next ...

*  Walking Slows the Progression of Alzheimer's Disease, Pitt Study Finds - :

... but not yet as severe as those found in Alzheimer's disease. About half of the people with MCI progress to Alzheimer's disease ... Alzheimer's disease is an irreversible, progressive brain disease that slowly destroys memory and cognitive skills. According ... "Because a cure for Alzheimer's is not yet a reality, we hope to find ways of alleviating disease progression or symptoms in ... Home Brain and Nerves Walking Slows the Progression of Alzheimer's Disease, Pitt Study Finds ...

*  MetLife Foundation Recognizes Alzheimer's Disease Research with Prestigious Awards

MetLife Foundation today announced the recipients of its 2012 Awards for Medical Research in Alzheimer's Disease: ... an educational initiative with the National Institute on Aging's Alzheimer's Disease Centers; the film Alzheimer's Disease: ... The staging of presymptomatic (preclinical) Alzheimer's disease in recently published National Institute on Aging-Alzheimer's ... our understanding of Alzheimer's disease and their dedication helps bring us closer to finding a cure for Alzheimer's disease. ...

*  Serotonin 5-HT2A receptor alterations in the postmortem neocortex of behaviorally assessed Alzheimer patients - Oxford...

Serotonin 5-HT2A receptor alterations in the postmortem neocortex of behaviorally assessed Alzheimer patients ... Serotonin 5-HT2A receptor alterations in the postmortem neocortex of behaviorally assessed Alzheimer patients ...

*  Single-Neuron Observations Mark Steps In Alzheimer's Disease - Redorbit

Multiple disease-related changes progress in parallel through distinct stages. Studying a mouse model of Alzheimer's disease, ... In addition to its well known, devastating effects on memory and learning, Alzheimer's disease can also impair a person's sense ... "That could have significant implications for future research in the field of Alzheimer's disease, as our findings raise the ... "An important conclusion from this study," Konnerth says, "is that the Alzheimer's disease-related changes on all levels - ...

*  Can An Eye Test Detect Early Alzheimer's Disease?

A study has found that an eye test may be able to identify Alzheimer's years before symptoms begin to show. ... Is there a new break in Alzheimer's research? ... Alzheimer's Disease. Alzheimer's disease is best known as the ... Can An Eye Test Detect Early Alzheimer's Disease?. By Orlin Sorensen on April 23, 2017 in Vision Conditions and Diseases ... Detecting Alzheimer's Through the Eyes. A new study has found that an eye exam could potentially detect Alzheimer's disease ...

*  Antibody reduces harmful brain amyloid plaques in Alzheimer's patients | (e) Science News

... it is clear that the disease commences with progressive amyloid deposition in the brains of affected persons between ten and ... Although the causes of Alzheimer's disease are still unknown, ... Although the causes of Alzheimer's disease are still unknown, ... 165 patients with early-stage Alzheimer's disease were treated in the phase 1b clinical trial. Although not initially planned ... Alzheimer's drug study gives 'tantalising' results. from BBC News: Science & Nature. Thu, 1 Sep 2016, 8:41:21 UTC ...

*  Resveratrol for Alzheimer's Disease - Full Text View -

Keywords provided by Alzheimer's Disease Cooperative Study (ADCS): Alzheimer's disease. Dementia. Brain diseases. Resveratrol. ... Alzheimer Disease. Dementia. Brain Diseases. Central Nervous System Diseases. Nervous System Diseases. Tauopathies. ... Alzheimer's Disease Cooperative Study Publications: Vang O, Ahmad N, Baile CA, Baur JA, Brown K, Csiszar A, Das DK, Delmas ... Change in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) [ Time Frame: Week 52 ]. The ADCS-ADL is ...

*  High Blood Pressure, Chest Pains Speed Up Progression of Alzheimer's Disease

Chest Pains Speed Up Progression of Alzheimer's Disease ST. PAUL, Minn. - People with Alzheimer's disease who have high blood ... High Blood Pressure, Chest Pains Speed Up Progression of Alzheimer's Disease. ST. PAUL, Minn. - EMBARGOED FOR RELEASE UNTIL 4 P ... The study involved 135 elderly people with newly diagnosed Alzheimer's disease who had annual cognitive tests for an average of ... "Many studies suggest that vascular factors are associated with an increased risk of developing Alzheimer's disease; these ...

*  Gentaur Molecular :Biochai \ cDNA Alzheimer's Disease Brain Frontal Lobe \ C1236051Alz

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*  Determinants of platelet activation in Alzheimer's disease. | IRIS Università degli Studi di Chieti

Determinants of platelet activation in Alzheimer's disease.. Autori interni: CIABATTONI, Giovanni. PORRECA, Ettore. DI IORIO, ... Conclusions Platelet activation is persistently enhanced in Alzheimer's disease. This is related, at least in part, to ... Conclusions Platelet activation is persistently enhanced in Alzheimer's disease. This is related, at least in part, to ... Objectives To investigate the rate of platelet thromboxane (TX) biosynthesis and its determinants in Alzheimer's disease. ...

*  A Systematic Review of Biomarkers for Disease Progression in Alzheimer's Disease

A systematic review was undertaken to determine what biomarkers for disease progression in Alzheimer's disease exist and how ... Studies of participants with probable Alzheimer's disease diagnosed by formal criteria were included. We made no restriction on ... evidence to recommend the use of any biomarker as an outcome measure for disease progression in Alzheimer's disease trials. ... A provisional 'roadmap' to improve the quality of future disease progression biomarker studies is presented. ...

*  IJMS | Free Full-Text | Diabetes Mellitus Induces Alzheimer's Disease Pathology: Histopathological Evidence from Animal Models

... is the major causative disease of dementia and is characterized pathologically by the accumulation of senile plaques (SPs) and ... Keywords: Alzheimer's disease; animal model; diabetes mellitus; insulin resistance; pathology Alzheimer's disease; animal model ... Alzheimer's disease (AD) is the major causative disease of dementia and is characterized pathologically by the accumulation of ... "Diabetes Mellitus Induces Alzheimer's Disease Pathology: Histopathological Evidence from Animal Models." Int. J. Mol. Sci. 17, ...

*  NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. - Helmholtz Zentrum für...

Alzheimer's disease were largely protected from loss of spatial memory and other sequelae associated with Alzheimer's disease, ... Alzheimer's disease were largely protected from loss of spatial memory and other sequelae associated with Alzheimer's disease, ... The NLRP3 inflammasome in Alzheimer's disease.Authors: Tan MS, Yu JT, Jiang T, Zhu XC, Tan L. Issue date: 2013 Dec ... NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice.. Authors:. Heneka, Michael T; Kummer, ...

*  News Round-Up July 2012 1st Edition - The Amazing World of Psychiatry: A Psychiatry Blog

The Amyloid Cascade hypothesis is commonly thought to be the best explanation for how Alzheimer's Disease arises. This Insulin ... Research published in the Journal of Alzheimer's Disease has provided further support for the hypothesis that Alzheimer's ... Disease may in part result from Insulin resistance in the brain. ... Research published in the Journal of Alzheimer's Disease has ... The Amyloid Cascade hypothesis is commonly thought to be the best explanation for how Alzheimer's Disease arises. This Insulin ...

*  Popcorn Plaque? Alzheimer Disease Is Slow, Yet Plaque Growth Is Fast | ALZFORUM

Popcorn Plaque? Alzheimer Disease Is Slow, Yet Plaque Growth Is Fast. Quick Links. *Article ... Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature. 2008 Feb 7;451( ... Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science. 2005 Feb 25;307(5713):1282-8. ... Paper: Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. ...

*  KEGG PATHWAY: Alzheimer's disease - Homo sapiens (human)

Alzheimer's disease - Homo sapiens (human) [ Pathway menu , Organism menu , Pathway entry , Download KGML , Show description , ... Alzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is ...

*  Study Evaluating The Efficacy And Safety Of Bapineuzumab In Alzheimer Disease Patients - Full Text View -

Alzheimer Disease. Dementia. Brain Diseases. Central Nervous System Diseases. Nervous System Diseases. Tauopathies. ... MedlinePlus related topics: Alzheimer's Disease Genetic and Rare Diseases Information Center resources: Familial Alzheimer ... Diagnosis of probable Alzheimer Disease (AD), with Mini Mental State Examination (MMSE) score of 16-26, and brain magnetic ... Study Evaluating The Efficacy And Safety Of Bapineuzumab In Alzheimer Disease Patients. This study has been terminated. ...

*  Alzheimer's Disease Research Center - University of Washington

The UW Alzheimer's Disease Research Center seeks to advance research in genetic risk, develop neuroimaging biomarkers for ... Addressing Alzheimer's Disease in Native American Communities/ The Tiny Worm Driving UW Alzheimer's Research/ This Summer's ... Alzheimer's Disease Research Center (ADRC), University of Washington. Core Leadership. Administrative Core, ADRC Director. ... Alzheimer's Disease Research Center - University of Washington An NIH-funded research resource center, associated with the UW ...

*  Study Examines Immunotherapy And Cerebrospinal Fluid Biomarkers In Patients With Alzheimer's Disease - Redorbit

Alzheimer disease (AD) is a progressive neurodegenerative disease characterized by, among other things, deposits of ... Immunotherapy with the antibody bapineuzumab in patients with mild to moderate Alzheimer disease resulted in decreases in a ... Study Examines Immunotherapy And Cerebrospinal Fluid Biomarkers In Patients With Alzheimer's Disease. by editor ... Bapineuzumab is an anti-Î β monoclonal antibody, and immunotherapy with antibodies against Î β is one of the major disease- ...

*  Corrections: Corrections - American Family Physician

In the article, "Treatment of Alzheimer Disease" (June 15, 2011, page 1403), the first clinical recommendation in the Strength ... "Acetylcholinesterase inhibitors should be considered first-line therapy for patients with mild to moderate Alzheimer disease," ... "Acetylcholinesterase inhibitors are modestly effective in patients with mild to moderate Alzheimer disease, although limited by ...

*  Frontiers | Role of endoplasmic reticulum Ca2+ signaling in the pathogenesis of Alzheimer disease | Frontiers in Molecular...

We argue that normalization of intracellular Ca2+ homeostasis could be a strategy for development of effective disease- ... We argue that normalization of intracellular Ca2+ homeostasis could be a strategy for development of effective disease- ... Alzheimer disease (AD) is a major threat of XXI century that is responsible for the majority of dementia in the elderly. ... Alzheimer disease (AD) is a major threat of XXI century that is responsible for the majority of dementia in the elderly. ...

*  Tobacco-derived compound prevents memory loss in Alzheimer's disease mice - :

About the Journal of Alzheimer's Disease (JAD). The Journal of Alzheimer's Disease is an international multidisciplinary ... Tropical diseases. 10/16/2017 Tropical diseases WHO supports the immunization of 874 000 people against yellow fever in Nigeria ... The Journal of Alzheimer's Disease has an Impact Factor of 3.82 according to Thomson Reuters' 2010 edition of Journal Citation ... Home Mental Health and Behavior Tobacco-derived compound prevents memory loss in Alzheimer's disease mice ...

Alzheimer's Disease Neuroimaging Initiative: Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a worldwide project that provides reliable clinical data for the research of pathology principle, prevention and treatment of Alzheimer’s disease (AD). Multiple research groups contribute their findings of the biological markers to the understanding of the progression of Alzheimer’s disease in the human brain.Senile plaquesTau protein: Tau proteins (or τ proteins, after the Greek letter by that name) are proteins that stabilize microtubules. They are abundant in neurons of the central nervous system and are less common elsewhere, but are also expressed at very low levels in CNS astrocytes and oligodendrocytes.Amyloid precursor proteinNeurofibrillary tangle: Neurofibrillary Tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary marker of Alzheimer's disease. Their presence is also found in numerous other diseases known as tauopathies.Amyloid precursor protein secretase: Secretases are enzymes that "snip" pieces off a longer protein that is embedded in the cell membrane.[of the amyloid precursor protein] Among other roles in the cell, secretases act on the amyloid precursor protein (APP) to cleave the protein into three fragments.Postoperative cognitive dysfunction: Postoperative cognitive dysfunction (POCD) is a short-term decline in cognitive function (especially in memory and executive functions) that may last from a few days to a few weeks after surgery. In rare cases, this disorder may persist for several months after major surgery.Familial British dementia: Familial British dementia is a form of dementia. It was first reported by Cecil Charles Worster-Drought in 1933 and is therefore also known as Worster-Drought syndrome.PresenilinAmyloid: Amyloids are insoluble fibrous protein [species|aggregates] sharing specific structural traits. They are insoluble and arise from at least 18 inappropriately folded versions of proteins and polypeptides present naturally in the body.Testicular atrophy: Testicular atrophy is a medical condition in which the male reproductive organs (the testes, which in humans are located in the scrotum) diminish in size and may be accompanied by loss of function. This does not refer to temporary changes, such as those brought on by cold.Repeatable Battery for the Assessment of Neuropsychological Status: The Repeatable Battery for the Assessment of Neuropsychological Status is a neuropsychological assessment initially introduced in 1998. It consists of ten subtests which give five scores, one for each of the five domains tested (immediate memory, visuospatial/constructional, language, attention, delayed memory).Fibril: Fibril is a fine fiber, such as a myofibril or neurofibril.Psychiatric assessment: A psychiatric assessment, or psychological screening, is a process of gathering information about a person within a psychiatric (or mental health) service, with the purpose of making a diagnosis. The assessment is usually the first stage of a treatment process, but psychiatric assessments may also be used for various legal purposes.Place cellCognitive skill: Cognitive functioning is a term referring to a human’s ability to process to (thoughts) that should not deplete on a large scale in healthy individuals. Cognition mainly refers to things like memory, the ability to learn new information, speech, understanding of written material.HyperintensityDennis Walsh: Dennis Walsh (12 June 1933 – 1 June 2005) was an English astronomer, born into a poor family in Manchester. He was best known for his discovery in 1979 of the first example of a gravitational lens which he made while studying quasars found in the Jodrell Bank 966MHz survey.MemantineRetroviral aspartyl protease: Retroviral aspartyl proteases are single domain aspartyl proteases from retroviruses, retrotransposons, and badnaviruses (plant dsDNA viruses). These proteases are generally part of a larger pol or gag polyprotein.HSD2 neurons: HSD2 neurons are a small group of neurons in the brainstem which are uniquely sensitive to the mineralocorticosteroid hormone aldosterone, through expression of HSD11B2. They are located within the caudal medulla oblongata, in the nucleus of the solitary tract (NTS).Nucleus basalis of Meynert: Nucleus basalis of Meynert, abbreviated NBM and also known as the nucleus basalis, is a group of neurons in the substantia innominata of the basal forebrain which has wide projections to the neocortex and is rich in acetylcholine and choline acetyltransferase.Memory clinic: A memory clinic is a dedicated medical clinic specialising in the assessment and diagnosis of memory disorders. Memory clinics were first seen in the UK in the 1980s, mainly in academic research centres.TBR1: T-box, brain, 1 is a transcription factor protein important in vertebrate embryo development. It is encoded by the TBR1 gene.Cerebral amyloid angiopathyMichael Chaplin (actor)Death of Ludwig van Beethoven: The death of Ludwig van Beethoven on 26 March 1827 followed a prolonged illness. It was witnessed by his sister-in-law and by his close friend Anselm Hüttenbrenner, who provided a vivid description of the event.Brain positron emission tomography: Positron emission tomography (PET) measures emissions from radioactively labeled metabolically active chemicals that have been injected into the bloodstream. The emission data are computer-processed to produce multi-dimensional images of the distribution of the chemicals throughout the brain.Tumor progression: Tumor progression is the third and last phase in tumor development. This phase is characterised by increased growth speed and invasiveness of the tumor cells.Lawn sweeper: A lawn sweeper, also known as a leaf sweeper, is a garden tool for the mechanical removal of debris, such as fallen leaves, pine needles, twigs, grass clippings or litter, from a lawn or paved area. Lawn sweepers operate via a rotating brush mechanism that sweeps up the debris and deposits it in a collection hopper for disposal.Gross pathology: Gross pathology refers to macroscopic manifestations of disease in organs, tissues, and body cavities. The term is commonly used by anatomical pathologists to refer to diagnostically useful findings made during the gross examination portion of surgical specimen processing or an autopsy.Centre for Research in Neurodegenerative DiseasesDonepezilColuracetam: Coluracetam (INN) (code name BCI-540; formerly MKC-231) is a nootropic agent of the racetam family. It was initially developed and tested by the Mitsubishi Tanabe Pharma Corporation for Alzheimer's disease.National Down Syndrome SocietyLewyClioquinolThiazolineBiomarkers of aging: Biomarkers of aging are biomarkers that better predict functional capacity at a later age than chronological age. Stated another way, biomarkers of aging would give the true "biological age", which may be different from the chronological age.Amnesia (Chumbawamba song): "Amnesia" is the second single from Chumbawamba's album Tubthumper, released on January 28, 1998. The song's lyrical content addresses the sense of betrayal that English leftists felt during the rise of New Labour.Brodmann area 38: Brodmann area 38, also BA38 or temporopolar area 38 (H), is part of the temporal cortex in the human brain. BA 38 is at the anterior end of the temporal lobe, known as the temporal pole.Psychomotor agitationNicolas LeblancNested case-control study: A nested case control (NCC) study is a variation of a case-control study in which only a subset of controls from the cohort are compared to the incident cases. In a case-cohort study, all incident cases in the cohort are compared to a random subset of participants who do not develop the disease of interest.Insulin-degrading enzyme: Insulin-degrading enzyme, also known as IDE is a human enzyme.TacrineExplicit memory: Explicit memory is the conscious, intentional recollection of previous experiences and information. People use explicit memory throughout the day, such as remembering the time of an appointment or recollecting an event from years ago.ANTH domain: A:21-299 A:19-285 A:19-285Hyperphosphorylation: Hyperphosphorylation occurs when a biochemical with multiple phosphorylation sites is fully saturated. Hyperphosphorylation is one of the signalling mechanisms used by the cell to regulate mitosis.Causes of Parkinson's disease: Parkinson's disease (PD) is a degenerative disorder of the central nervous system. Most people with PD have idiopathic Parkinson's disease (having no specific known cause).Silent mutation: Silent mutations are mutations in DNA that do not significantly alter the phenotype of the organism in which they occur. Silent mutations can occur in non-coding regions (outside of genes or within introns), or they may occur within exons.GalantamineQRISK: QRISK2 (the most recent version of QRISK) is a prediction algorithm for cardiovascular disease (CVD) that uses traditional risk factors (age, systolic blood pressure, smoking status and ratio of total serum cholesterol to high-density lipoprotein cholesterol) together with body mass index, ethnicity, measures of deprivation, family history, chronic kidney disease, rheumatoid arthritis, atrial fibrillation, diabetes mellitus, and antihypertensive treatment.Frontotemporal lobar degeneration: Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes.BenzothiazoleNeurocalcin: Neurocalcin is a neuronal calcium-binding protein that belongs to the neuronal calcium sensor (NCS) family of proteins. It expressed in mammalian brains.AmyloidosisSORL1: Sortilin-related receptor, L(DLR class) A repeats containing is a protein that in humans is encoded by the SORL1 gene.Inferior longitudinal fasciculus: The inferior longitudinal fasciculus connects the temporal lobe and occipital lobe, running along the lateral walls of the inferior and posterior cornua of the lateral ventricle.Infinite alleles model: The infinite alleles model is a mathematical model for calculating genetic mutations. The Japanese geneticist Motoo Kimura and American geneticist James F.Glycogen synthase kinase: Glycogen synthase kinase is an enzyme.Agonal respiration: Agonal respiration, gasping respiration or agonal breathing is an abnormal pattern of breathing and brainstem reflex characterized by gasping, labored breathing, accompanied by strange vocalizations and myoclonus. Possible causes include cerebral ischemia, extreme hypoxia or even anoxia.Matrix model: == Mathematics and physics ==EC-hippocampus system: The Entorhinal Cortex (EC) is a major part of the hippocampal formation of the human brain, and is reciprocally connected with the hippocampus.

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

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)

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

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)

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

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)

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

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)

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

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)

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

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)

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

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)

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

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)


  • Abnormally phosphorylated tau protein in senile dementia of Lewy body type and Alzheimer disease: evidence that the disorders are distinct. (
  • The relationship between Alzheimer disease (AD) and dementia with Lewy bodies (senile dementia Lewy body type, or SDLT) and dementia in Parkinson's disease is unclear. (
  • Binswanger's disease (BD), also called subcortical vascular dementia, is a type of dementia caused by widespread, microscopic areas of damage to the deep layers of white matter in the brain. (
  • Posterior cortical atrophy may be associated with Alzheimer's disease, Lewy body dementia or other neurological conditions. (
  • Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. (
  • It lies between the normal memory loss of aging and the more serious conditions of dementia and Alzheimer's disease . (

Alzheimer's Disease

  • Other symptoms include forgetfulness (but not as severe as the forgetfulness of Alzheimer's disease), changes in speech, an unsteady gait, clumsiness or frequent falls, changes in personality or mood (most likely in the form of apathy, irritability, and depression), and urinary symptoms that aren't caused by urological disease. (
  • BD can often coexist with Alzheimer's disease. (
  • Mayo Clinic's campus in Arizona is part of the Arizona Alzheimer's Consortium, a statewide research collaboration that studies ways to detect, treat and prevent Alzheimer's disease and related conditions. (
  • Determinants of platelet activation in Alzheimer's disease. (
  • Objectives To investigate the rate of platelet thromboxane (TX) biosynthesis and its determinants in Alzheimer's disease. (
  • Conclusions Platelet activation is persistently enhanced in Alzheimer's disease. (
  • September 18, 2017 - The UW ADRC seeks proposals for one-year pilot projects that use its resources to advance the understanding, diagnosis, and/or treatment of Alzheimer's disease. (
  • Examination by trained medical personnel is required to ensure proper diagnosis and treatment of Alzheimer's disease and other related disorders. (


  • Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. (


  • Vascular cognitive impairment (VCI) is a heterogeneous disease that is caused by a wide variety of vascular factors. (
  • The term subcortical ischemic vascular disease is often used for both lacunar state and white matter disease, but there may be different pathophysiologies involved, particularly when there is cerebral hypoperfusion, which has a major effect on the vulnerable deep white matter. (
  • Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. (
  • Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. (


  • 2 , 3 Large-vessel disease leads to strokes with a stepwise course as a result of multiple infarctions that result in concomitant loss of intellect. (


  • Methods and results A cross-sectional comparison of urinary 11-dehydro-TXB2 and 8-iso-prostaglandin (PG)F2α (markers of in vivo platelet activation and lipid peroxidation, respectively), plasma Vitamin E, C-reactive protein (CRP), tumor necrosis factor (TNF)-α and interleukin (IL)-6, was carried-out in 44 Alzheimer patients and 44 matched controls. (


  • German Center for Neurodegenerative Diseases (DZNE), Munich, Germany (M.D. (


  • Brain imaging, which reveals the characteristic brain lesions of Binswanger's disease, is essential for a positive diagnosis. (


  • Binswanger disease (BD) was first described in 1894 in patients with arteriolosclerotic demyelination. (
  • To investigate the cyclooxygenase (COX)-isoform involved in TXA2 biosynthesis, nine Alzheimer patients were treated with low-dose aspirin (100 mg/d) or rofecoxib (25 mg/d) for 4 days. (
  • 11-dehydro-TXB2: Rs = −0.44, p = 0.0026) in Alzheimer patients. (



  • Furthermore subjects are not eligible if they were diagnosed with idiopathic Parkinson's Disease (PD), with persistent severe depression, normal pressure hydrocephalus, multiple system atrophy, cortico-basal degeneration or Huntington's Chorea Disease. (


  • Cortical homogenates from 12 cases each of AD and SDLT, 13 cases of Parkinson's disease, and 11 normal controls were examined by Western blot analysis with antibodies that detect PHF-tau. (


  • No PHF-tau was found in Parkinson's disease or control cortex. (



  • Small-vessel disease has several forms: it may either produce lacunes mainly in the basal ganglia without white matter damage or extensive changes in the white matter with or without lacunes (Table I in the online-only Data Supplement). (