Rare locus and neurodegenerative disease disease susceptibility. Medical search. Frequent questions

Advances in genomic technologies and statistical methods have converged to allow the discovery of susceptibility loci for complex genetic traits, and the field now confronts the enormous challenge to confirm the responsible genes and define their functions in the biology of health and disease. (bcm.edu)
In addition to the potential for fundamental biological insights, functional dissection of susceptibility genes will be essential to realize the full promise of human genetics for clinical applications. (bcm.edu)
Most notably, rare pathogenic mutations have been identified in the amyloid precursor protein, microtubule associate protein tau, and alpha-synuclein genes, encoding the primary constituents of the defining disease pathologies (amyloid plaques and Tau neurofibrillary tangles in AD, and Lewy bodies in PD, respectively). (bcm.edu)
Based on the "common disease-common variants hypothesis", genome-wide association studies (GWAS) have been extensively conducted to identify disease-susceptible genes. (jnss.org)
Although GWAS have successfully revealed numerous susceptibility genes for neurological diseases, odds ratios associated with these risk alleles are generally low and account for only a small portion of estimated heritability. (jnss.org)
Identifying and studying genes that contribute to Alzheimer s disease (AD) development will help us to understand the causes of AD, providing the basis for developing new treatments. (neurodegenerationresearch.eu)
Common variation in nine novel genes are known to increase susceptibility to AD. (neurodegenerationresearch.eu)
However, these genes can not account for the overall inheritance of susceptibility to POAG pathogenesis. (molvis.org)
Many causative genes and susceptibility loci have been identified to be associated with Parkinson's disease (PD) in different ethnic populations. (paparesearch.com)
Here, we tested the degree to which risk for ALS was affected by rare variants in ALS genes, polygenic risk score, or both. (cdc.gov)
An approach for ranking genes implicated in the comorbid condition of the two diseases was proposed. (biomedcentral.com)
The approach is based on ten criteria for ranking genes by their importance, including relevance scores of association between disease and genes, standard methods of gene prioritization, as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analyzed genes. (biomedcentral.com)
According to the proposed approach, the genes OPRM1, CHRNA4 and SNCA had the highest priority in the development of comorbidity of these two diseases. (biomedcentral.com)
We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. (amsterdamumc.org)
The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. (amsterdamumc.org)
In secondary analyses designed to highlight the specific genes driving the aggregate signal, we confirmed associations at the GBA and SMPD1 loci and newly implicate CTSD, SLC17A5, and ASAH1 as candidate Parkinson's disease susceptibility genes. (amsterdamumc.org)
Nature Genetics) of the first new susceptibility genes for 17 years defined a pivotal moment in Alzheimer's genetics research. (cardiff.ac.uk)
What is striking about her group's findings is that the genes identified show patterns of relationship, which implicate novel disease mechanisms, including immunity, endocytosis, lipid transport and ubiquination. (cardiff.ac.uk)
2018). Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. (harvard.edu)
The study was based on a hypothesis that some individuals have an underlying susceptibility to developing PML, based on the presence of variants in genes that are important in the immune system. (medicalresearch.com)
Traditional linkage analysis, gene cloning and Genome Wide Association Studies (GWAS) have identified several loci and genes associated with monogenic PD. (acnr.co.uk)
In addition, heterozygote mutations in certain 'recessive' genes have been associated with late onset disease, possibly because of partial expression of the corresponding protein. (acnr.co.uk)
We totally identified 141 pathogenic variant loci of 129 genes in these 34 pSS-PAH patients, using WES analysis. (biomedcentral.com)
The candidate pathogenic genes may be the potential genetic markers for early warning of this disease. (biomedcentral.com)

The very low incidence of G2019S mutation in Egyptians living in Upper Egypt compared to Egyptians inhabitants in North Egypt suggests a prospective multicenter study on a large number of Egyptians with Parkinson's disease to reach a real incidence of that mutation and if it has (or not) a correlation to causation and course of Parkinson's disease among Egyptians. (paparesearch.com)
Parkinson's Disease is the second most common neurodegenerative disease, after Alzheimer's. (ukessays.com)
Parkinson's Disease (PD) is characterized clinically by tremors at rest, bradykinesia (slowness of voluntary movement), muscle rigidity, decrease in postural reflex and facial expression and an altered gait (Kumar et al. (ukessays.com)
This review will summarize the updated research progress on APOE functions and its role in Alzheimer's disease, Parkinson's disease, cardiovascular diseases, multiple sclerosis, type 2 diabetes mellitus, Type III hyperlipoproteinemia, vascular dementia, and ischemic stroke. (dovepress.com)
3 In this review, we discuss the biological functions of human APOE and its role in Alzheimer's disease (AD), Parkinson's disease (PD), cardiovascular diseases (CVD), multiple sclerosis (MS), type 2 diabetes mellitus (T2DM), vascular dementia (VD), and ischemic (occlusive) stroke (IS). (dovepress.com)
Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. (amsterdamumc.org)
We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk. (amsterdamumc.org)
In our discovery cohort, the majority of Parkinson's disease cases (56%) have at least one putative damaging variant in a lysosomal storage disorder gene, and 21% carry multiple alleles. (amsterdamumc.org)
Our results highlight several promising new susceptibility loci and reinforce the importance of lysosomal mechanisms in Parkinson's disease pathogenesis. (amsterdamumc.org)
We suggest that multiple genetic hits may act in combination to degrade lysosomal function, enhancing Parkinson's disease susceptibility. (amsterdamumc.org)
AD and Parkinson's disease, ALS, schizophrenia) and complex statistical analyses (e.g. gene-wide/burden, pathway analyses). (cardiff.ac.uk)
This study was meant to address the gap that current oral levodopa formulations do not suffice to lessen motor fluctuations in people with Parkinson's disease. (medicalresearch.com)
The increase in TMEM106B levels with ageing was specific to carriers of the rs1990622-A allele in the TMEM106B gene that increases risk for frontotemporal dementia, Alzheimer's disease, Parkinson's disease, and hippocampal sclerosis with ageing. (biomedcentral.com)
Although we are learning more each day about the pathophysiology of Parkinson's disease, it is still considered largely idiopathic (of unknown cause). (atrainceu.com)
Physiologically, the symptoms associated with Parkinson's disease are the result of the loss of a number of neurotransmitters, most notably dopamine. (atrainceu.com)
As less and less dopamine is produced by the neurons affected by Parkinson's disease, far less dopamine is available to bind to the dopamine receptors on the post-synaptic membrane. (atrainceu.com)
In Parkinson's disease the loss occurs at a much greater rate and both biochemical measures and imaging studies suggest there is a significant decrease in dopamine by the time motor symptoms appear. (atrainceu.com)
In this view, Parkinson's disease is an accelerated version of the cell death seen with normal aging (Cookson, 2009). (atrainceu.com)
Diana Olszewska is a Neurology Research Fellow at the Dublin Neurological Institute, Mater Misericordiae University Hospital with a particular interest in genetics of Parkinson's disease. (acnr.co.uk)
His areas of interest include Parkinson's disease, atypical dementias and the genetics of neurological disorders. (acnr.co.uk)
Parkinson's disease (PD) is a heterogeneous, neurodegenerative disorder affecting 6.3 million people worldwide and 1.2 million in Europe. (acnr.co.uk)
GWAS and linkage analysis have identified 18 Parkinson's disease loci (PARK) numbered in a chronological order. (acnr.co.uk)
Parkinson's disease is a progressive neurodegenerative disorder, where most cases are sporadic with a late onset. (biomedcentral.com)
Enhanced mTORC1 signaling and protein synthesis in pathologic α-synuclein cellular and animal models of Parkinson's disease. (neurotree.org)
DNA Methylation Signature of Aging: Potential Impact on the Pathogenesis of Parkinson's Disease. (neurotree.org)
The c-Abl inhibitor IkT-148009 suppresses neurodegeneration in mouse models of heritable and sporadic Parkinson's disease. (neurotree.org)
Cell Biology of Parkin: Clues to the Development of New Therapeutics for Parkinson's Disease. (neurotree.org)

In the coming years, with the completion of the largest possible genetic meta-analyses along with the advent of whole-genome sequencing, our knowledge of common and rare susceptibility variants will rapidly expand, implicating vast genetic networks including hundreds of loci in neurologic diseases. (bcm.edu)
The clinical manifestation of neurodegenerative disease is the culmination of a multi-tiered pathogenic cascade that evolves over decades-understanding how genetic variants impact this causal chain is essential. (bcm.edu)
Substantial evidence supports a model in which many genetic variants promote the development of neuropathology, subsequently leading to the clinical manifestations of disease. (bcm.edu)
Since the power of detection of rare alleles by GWAS employing common SNPs is limited, comprehensive genome sequencing is required to identify these rare variants. (jnss.org)
Based on large-scale case-control studies, we demonstrated that a common variant and multiple rare variants of COQ2, both of which are functionally impaired, are associated with an increased risk of sporadic MSA. (jnss.org)
Supplementation with CoQ10 may be helpful in treating MSA, particularly for those with susceptibility-conferring COQ2 variants. (jnss.org)
However, these variants only account for roughly 32% of the genetic aetiology of the disease. (neurodegenerationresearch.eu)
Next generation sequencing (NGS) allows the identification and analysis of rare variants (RV). (neurodegenerationresearch.eu)
This paper provides a brief presentation on the genetics of multiple sclerosis susceptibility and on current work that uncovers the cellular effects, immunological and non-immunological, associated with genetic risk variants. (researchgate.net)
Although there has been much success in identifying genetic variants associated with common diseases using genome-wide association studies (GWAS), it has been difficult to demonstrate which variants are causal and what role they have in disease. (researchgate.net)
Moreover, the modest contribution that these variants make to disease risk has raised questions regarding their medical relevance. (researchgate.net)
As with many other complex diseases, risk of developing MS is driven by multiple common variants whose biological effects are not immediately clear. (researchgate.net)
From the abstract: 'The genetic etiology of amyotrophic lateral sclerosis (ALS) includes few rare, large-effect variants and potentially many common, small-effect variants per case. (cdc.gov)
Independently, rare variants in NUP50 were associated with ALS risk (P? (cdc.gov)
2013). Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington's disease motor onset . (up.pt)
On 09/13/17, NIH grant R01 MH101244 "Rare and common variants in complex disease" (4 PIs: Sunyaev/Price/Kraft/Neale) was awarded to Alkes Price as a subcontract with BWH (Shamil Sunyaev)/NIMH. (harvard.edu)
Although genetic variants identified in this way are enormously informative about pathways that affect disease processes and that can, when perturbed, modify disease phenotypes [ 25 - 30 ], they are likely to be different from the naturally occurring variations. (biomedcentral.com)
Pathogenic variants in the Longitudinal Early-onset Alzheimer's Disease Study cohort Alzheimers Dement. (usc.edu)

In amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, these barriers become hyperpermeable, allowing a wider variety of molecules to pass through leading to more severe and more rapidly progressing disease. (hindawi.com)
We investigate the use of wearable sensors, worn on four limbs at home during natural behavior, to quantify motor function and disease progression in 376 individuals with amyotrophic lateral sclerosis. (cdc.gov)
Amyotrophic lateral sclerosis (ALS) is an adult-onset, fatal neurodegenerative syndrome characterised mainly by the progressive loss of upper and lower motor neurons and their axons resulting in wasting, paresis and death from respiratory failure within a few years on average. (bmj.com)

Here we have investigated a single nucleotide polymorphism (SNP) in the TNFRSF1A gene, that encodes tumour necrosis factor receptor 1 (TNFR1), which was discovered through GWAS to be associated with multiple sclerosis (MS), but not with other autoimmune conditions such as rheumatoid arthritis, psoriasis and Crohn's disease. (researchgate.net)
Hence, our study demonstrates that clinical practice can be informed by comparing GWAS across common autoimmune diseases and by investigating the functional consequences of the disease-associated genetic variation. (researchgate.net)
Multiple genome-wide association studies (GWAS) over the past 10 years have uncovered more than 200 loci that independently contribute to disease pathogenesis. (researchgate.net)

2018). Leveraging molecular quantitative trait loci to understand the genetic architecture of diseases and complex traits. (harvard.edu)

Although MSA has been defined as a non-genetic disorder until recently, several multiplex MSA families have been reported, indicating that strong genetic factors confer susceptibility to the disease in multiplex families. (jnss.org)
Alzheimer's disease (AD) is the most common cause of dementia in the elderly, whereas frontotemporal lobar degeneration (FTLD) is the most frequent neurodegenerative disorder with a pre-senile onset. (touchneurology.com)
Alzheimer disease (AD) is a neurodegenerative disorder marked by cognitive and behavioral impairment that significantly interferes with social and occupational functioning. (medscape.com)

This review focuses on the current knowledge of the pathogenesis of the inflammatory and neurodegenerative elements of the multiple sclerosis plaque. (researchgate.net)
Evidence for CD4 + T-cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol signaling to CD4 + T lymphocytes is summarized to support the thesis that calcitriol is sunlight's main protective signal transducer in autoimmune disease risk. (frontiersin.org)
Genetic association studies aimed at defining susceptibility to POAG may provide important insights into the pathogenesis of POAG. (molvis.org)
Despite this evidence, the BSCB (like the BBB) breakdown in disease pathogenesis remains unclear [ 6 , 7 ]. (hindawi.com)
PAH is a rare and severe complication of pSS with poor prognosis [ 4 ] and the pathogenesis of pSS-associated PAH (pSS-PAH) is unclear yet. (biomedcentral.com)

Author of 85 papers on International indexed (IF) journals, 10 chapters in books and over 100 Abstracts, mainly in the field of HLA immunogenetics and of the genetics of autoimmune and neurodegerative diseases. (neidos.it)
Scholz SW, Bras J. Genetics underlying atypical parkinsonism and related neurodegenerative disorders. (jamanetwork.com)

Although these mutations themselves are causative, many disease characteristics such as age of onset, penetrance, and severity of specific symptoms can vary widely between individuals. (biomedcentral.com)
This classification is imperfect as it contains both confirmed and unconfirmed loci (loci not replicated) and the causative gene remains unknown for many loci. (acnr.co.uk)

The goal is to understand how discrete developmental events contribute to physiological diversity in cognitive performance, or affective susceptibility to stress, and understand the neurodevelopmental basis of neurologic diseases. (igbmc.fr)

Histological brain sections of PD patients shows characteristic, large inclusion bodies in the cytosol of surviving neurons of the substantia nigra, as well as locus ceruleus and surrounding brainstem nuclei, called Lewy bodies (Kumar et al. (ukessays.com)
Tau-positive neuronal inclusions in neurons of the substantia nigra (no alpha synuclein-positive inclusions, as are found in Parkinson disease). (medscape.com)
One more scenario (not shown) of PD motor symptom development involves possible in utero environmental toxicants or genetic factors leading to an atypically low number of dopaminergic neurons at birth and increased susceptibility to PD development (Haas et al. (atrainceu.com)

Multiple sclerosis is a demyelinating neurodegenerative disease with a strong genetic component. (researchgate.net)
Multiple sclerosis (MS) is a common autoimmune disease that targets myelin in the central nervous system (CNS). (researchgate.net)
Evidence linking sunlight, vitamin D, and the risk of multiple sclerosis and type 1 diabetes is summarized to develop the thesis that vitamin D is the environmental factor that most strongly influences autoimmune disease development. (frontiersin.org)
The global burden has risen with the near tripling in the last half-century of multiple sclerosis (MS) ( 2 , 3 ), type 1 diabetes (T1D) ( 4 ), and other autoimmune diseases. (frontiersin.org)
Multiple sclerosis and T1D have distinct target organs, genetic risk factors, onset ages, and female to male ratios, but target organ-specific T cells as initiators unite these diseases. (frontiersin.org)
D'Alfonso S. No evidence of association of the rare nsSNP rs35667974 in IFIH1 with multiple sclerosis. (neidos.it)
D'Alfonso S. HLA-class I markers and multiple sclerosis susceptibility in the Italian population. (neidos.it)

A 3'-untranslated region variant is associated with impaired expression of CD226 in T and natural killer T cells and is associated with susceptibility to systemic lupus erythematosus. (neidos.it)
Promoter insertion/deletion in the IRF5 gene is highly associated with susceptibility to systemic lupus erythematosus in distinct populations, but exerts a modest effect on gene expression in peripheral blood mononuclear cells. (neidos.it)

2017). Rare neurodegenerative diseases: Clinical and genetic update . (up.pt)

Importantly, TNF-blocking drugs can promote onset or exacerbation of MS, but they have proven highly efficacious in the treatment of autoimmune diseases for which there is no association with rs1800693. (researchgate.net)
This review highlights recent advances in vitamin D and T-lymphocyte biology in an effort to harness vitamin D's potential to reduce the impact of autoimmune diseases. (frontiersin.org)
Autoimmune diseases represent a failure of self-identification leading to an immune-mediated assault on host tissues. (frontiersin.org)
We drew mainly on MS and T1D research because intensive investigation has generated detailed insights into vitamin D mechanisms in these diseases and provided valuable guidance for research on other autoimmune diseases. (frontiersin.org)
Other autoimmune diseases are included where robust mechanistic data exist. (frontiersin.org)
A recent chapter ( 6 ) and a review ( 7 ) have summarized vitamin D mechanisms in autoimmune diseases more generally. (frontiersin.org)
We have ongoing interests in the systems level analysis and reconstruction of regulatory networks, inference of enhancer-promoter contacts, predictive models of gene expression and integration of three-dimensional chromatin structure with one-dimensional epigenetic measurements in the context of cancer, malaria, asthma and several autoimmune diseases. (ucsd.edu)

Through tracing the disease ancestry and "mutational history", as well as a study of thousands of Indian families, Mukerji and her team were able to get a better understanding of the underlying genetic mechanisms that cause ataxias and develop a clinical screening to be able to check disease susceptibility of healthy patients. (wikipedia.org)
This indicates that the clinical experience with these drugs parallels the disease association of rs1800693, and that the MS-associated TNFR1 variant mimics the effect of TNF-blocking drugs. (researchgate.net)
Correspondingly, the clinical strategies available for the management of the disease have widened. (researchgate.net)
Departments of pharmacology, neurology, and clinical pathology, Assiut University (Egypt) and Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany between June 2010 and September 2011. (paparesearch.com)
Pathological processes leading to Alzheimer disease (AD) begin many years before clinical diagnosis, hence efficient prevention should be initiated very early. (u-bordeaux.fr)
Monogenic gain-of-function protein aggregation diseases, including Huntington's disease, exhibit substantial variability in age of onset, penetrance, and clinical symptoms, even between individuals with similar or identical mutations. (biomedcentral.com)
The aim of this study was to explore the genetic susceptibility of pSS-PAH and to establish a preliminary understanding on the association between genotypes and clinical phenotypes. (biomedcentral.com)
Although SOD1 mutations have been identified in many western populations at comparable frequencies, screening in clinical practice suggests that these mutations are rare in The Netherlands. (bmj.com)

Until recently, our understanding of the genetic causes for human diseases were largely limited to the study of extreme phenotypes produced by Mendelian disorders. (bcm.edu)
The majority of patients have sporadic disease.6 Although the true Mendelian forms of PD are rare (occuring in 30% of familial and 3-5% of sporadic PD) 5 there is a positive family history in 10% of patients with apparently sporadic PD. (acnr.co.uk)

These studies take advantage of murine models relevant to neurodevelopmental disorders, Parkinson and Huntington diseases, and depression . (igbmc.fr)
Most PIDs are relatively rare disorders. (lu.se)
The incidence of PIDs varies greatly from about 1:500 births with selective IgA deficiency to only a few known cases for the rarest disorders. (lu.se)

During the past three decades, we have witnessed remarkable advances in understanding the molecular bases of hereditary neurological diseases by "positional cloning" strategies. (jnss.org)
The molecular bases of sporadic neurological diseases, however, largely remain unknown. (jnss.org)
We also investigate the therapeutic potential of specific retinoids in neurological and psychiatric diseases. (igbmc.fr)

Linkage analyses of 6 multiplex MSA families revealed several loci showing positive heterogeneity lod (HLOD) scores. (jnss.org)
Much of the current knowledge about modifiers of conformational diseases has been gathered from linkage/association studies, candidate approaches, and unbiased genetic screens. (biomedcentral.com)

The neuronal injuries associated with Alzheimer disease have several similarities with the optic nerve changes often seen with POAG. (molvis.org)
Primary open angle glaucoma (POAG) is a multifactorial neurodegenerative disease. (molvis.org)
Primary open angle glaucoma (POAG), the most common form of glaucoma in the Western world, is an age-related, complex disease characterized by progressive irreversible degeneration of the optic nerve due to apoptotic retinal ganglion cell death [2] . (prolekarniky.cz)

The availability of next-generation sequencing technologies has made it possible to explore molecular bases of sporadic diseases. (jnss.org)
We investigated the same mutation in 69 Egyptian patients with sporadic PD and 96 ethnically matched controls who all were inhabitants of Upper Egypt to find out if it could be a susceptibility gene for PD among Egyptians. (paparesearch.com)
Concerning sporadic AD, it is known that the presence of the ε4 allele of the apolipoprotein E gene is a susceptibility factor. (touchneurology.com)
The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort Alzheimers Dement. (usc.edu)
Although the onset of PD is, in most cases, considered to be sporadic, individuals with a first-degree relative with PD are at greater risk of developing disease. (biomedcentral.com)
In the remaining 90% of ALS patients where there is no family history, the disease is considered to be sporadic (denoted as SALS). (bmj.com)

The scope is to evaluate if the new acquisitions may change the rehabilitation approaches to schizophrenia modifying the balance about the neurodevelopmental hypothesis of schizophrenia accepting that the cognitive deficits are produced by errors during the normal development of the brain (neurodevelopmental hypothesis) that remains stable in the course of illness and the neurodegenerative hypothesis according of which they derived from a degenerative process that goes on inexorably. (clinical-practice-and-epidemiology-in-mental-health.com)

Apoptotic cell death in disease-Current understanding of the NCCD 2023. (neurotree.org)

2016). (CAG) n loci as genetic modifiers of age-at-onset in patients with Machado-Joseph disease from mainland China . (up.pt)

Inheritance of the TNF-α (−863) C allele has been associated with an elevated risk of Alzheimer disease. (molvis.org)
Targeting APOE may be a potential approach for diagnosis, risk assessment, prevention, and treatment of various neurodegenerative and cardiovascular diseases in humans. (dovepress.com)
Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. (prolekarniky.cz)
Since then, the consortium she leads, GERAD (Genetic and Environmental Risk in Alzheimer's Disease), has continued the momentum and has played a leading role in further discoveries. (cardiff.ac.uk)
2011). The APOE ε 2 allele increases the risk of earlier age at onset in Machado-Joseph disease . (up.pt)
2018) Detecting genome-wide directional effects of transcription factor binding on polygenic disease risk. (harvard.edu)
Comparison of genetic and health risk factors for mild cognitive impairment and Alzheimer's disease between Hispanic and non-Hispanic white participants Alzheimers Dement. (usc.edu)

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, with a prevalence of 5% after 65 years of age. (touchneurology.com)
Alzheimer disease (AD) is the most common progressive degenerative form of dementia, strongly associated with advancing age. (medscape.com)

Indeed, "functional and mechanistic work on the molecular etiology of disease remains one of the major challenges in modern biology" ( 5 ). (frontiersin.org)
All the proposed and approved treatments aim to slow a patient's rate of functional decline and prolong life, but reversing damage in neurodegenerative conditions is a more elusive goal. (cdc.gov)

There are also rare cases of early-onset Parkinson's, which are usually familial. (ukessays.com)
Research into the gene mutations discovered in such hereditary cases has also contributed to the understanding of the aetiology of the spontaneous, late onset form of the disease. (ukessays.com)
2012). CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion . (up.pt)
Introgression of polyQ40 into three wild genetic backgrounds uncovered wide variation in onset of aggregation and corresponding toxicity, as well as alteration in the cell-specific susceptibility to aggregation. (biomedcentral.com)
Amyloid and tau-PET in early-onset AD: Baseline data from the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Alzheimers Dement. (usc.edu)
Influence of amyloid and diagnostic syndrome on non-traditional memory scores in early-onset Alzheimer's disease Alzheimers Dement. (usc.edu)
Sex and APOE e4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease Alzheimers Dement. (usc.edu)
Cerebrospinal fluid biomarkers in the Longitudinal Early-onset Alzheimer's Disease Study Alzheimers Dement. (usc.edu)
White matter hyperintensities are higher among early-onset Alzheimer's disease participants than their cognitively normal and early-onset nonAD peers: Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Alzheimers Dement. (usc.edu)
Baseline neuropsychiatric symptoms and psychotropic medication use midway through data collection of the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) cohort Alzheimers Dement. (usc.edu)
Profiling baseline performance on the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) cohort near the midpoint of data collection Alzheimers Dement. (usc.edu)
In rare incidences familial forms of early-onset parkinsonism occur, and when recessively inherited, cases are often explained by mutations in either the parkin (PARK2) or PINK1 (PARK6) gene or on exceptional occasions the DJ-1 (PARK7) or ATP13A2 (PARK9) gene. (biomedcentral.com)

The disease was originally described by Alois Alzheimer and Gaetano Perusini in 1906, and it is clinically characterised by progressive cognitive impairment including impaired judgement, decision-making and orientation, often accompanied, in later stages, by psychobehavioural disturbances as well as language impairment. (touchneurology.com)

Our findings provide preliminary data of exome sequencing to identify susceptibility loci for pSS-PAH and enriched our understanding of the genetic etiology for pSS-PAH. (biomedcentral.com)

We sought to determine if mobile applications (apps) and wearable devices can be used to quantify ALS disease progression through active (surveys) and passive (sensors) data collection. (cdc.gov)
Parkinson's is increasingly seen as a complex neurodegenerative disease with a sequence of progression. (atrainceu.com)
In this review, we explore the role of biological sex in the development of the brain and analyze its impact on the predisposition toward and the progression of neurodegenerative diseases. (mdpi.com)

Animal models of the disease, created using neurotoxins such as rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or transgenic mice that overexpress human SYN gene (for ï ¡-synuclein) mutations, do not faithfully replicate the structure and antigenicity of the Lewy bodies found in PD (Dickson 2001). (ukessays.com)
Understanding the mutations in APOE, their structural properties, and their isoforms is important to determine its role in various diseases and to advance the development of therapeutic strategies. (dovepress.com)
Conclusions The authors demonstrate that SOD1 mutations are rare in The Netherlands in familial and SALS. (bmj.com)
Mutational analysis revealed point-mutations in the SOD1 gene to cosegregate with the disease in these pedigrees. (bmj.com)

There is strong evidence that it first affects the dorsal motor nucleus of the vagus nerve and the olfactory bulbs and nucleus, then the locus coeruleus, and eventually the substantia nigra. (atrainceu.com)

Multiple system atrophy (MSA) is a progressive neurodegenerative disease with 12,000 patients in Japan, which is clinically characterized by autonomic failure in addition to various combinations of parkinsonism, and cerebellar ataxia. (jnss.org)

The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022 Alzheimers Dement. (usc.edu)

Although Alzheimer disease (AD) is more frequent in individuals with Down syndrome (DS), the main contributing factor is unknown. (medscape.com)
Pulmonary arterial hypertension (PAH) is a rare complication of primary Sjögren's syndrome (pSS). (biomedcentral.com)
Primary Sjögren's syndrome (pSS) is an autoimmune connective tissue disease (CTD) characterized by exocrine gland dysfunction, resulting predominately in dryness of the mouth and eyes [ 1 ]. (biomedcentral.com)

however, many individuals have IOP elevation without optic nerve disease [6] , and at least 33% of affected individuals have progressive retinal ganglion cell loss despite IOP measurements in the normal range (less than 22 mmHg), a condition defined as normal-pressure glaucoma (NPG) [7] . (prolekarniky.cz)

To address this, we examined the role of natural variation in defining the susceptibility of genetically diverse individuals to protein aggregation and toxicity, using the Caenorhabditis elegans polyglutamine model. (biomedcentral.com)
Resistance to protein aggregation and the ability to restrict its associated cellular dysfunction are independently controlled by the natural variation in genetic background, revealing important new considerations in the search for targets for therapeutic intervention in conformational diseases. (biomedcentral.com)

A better understanding of ALS should lead to earlier detection and treatment, stopping or slowing the disease before patients develop a severe, progressive loss of motor function. (cdc.gov)
The course of the disease is highly variable, with some patients exhibiting very few symptoms as they age and others whose symptoms progress rapidly. (atrainceu.com)
Patients with PID have increased susceptibility to recurrent and persistent infections, but other symptoms are also common. (lu.se)

A deep understanding of molecular mechanisms relevant to gene-environment interactions is needed to deliver etiology-based autoimmune disease prevention and treatment strategies. (frontiersin.org)
A deep understanding of disease mechanisms will be needed to deliver etiology-based strategies to reverse this vexing trend. (frontiersin.org)
Gene-environment interactions, sunlight and vitamin D, and T lymphocytes as autoimmune disease initiators and vitamin D targets are discussed to explain the rationale for reviewing vitamin D mechanisms in T cells. (frontiersin.org)
Finally, unanswered questions relating to vitamin D mechanisms in CD4 + T cells are highlighted to promote further research that may lead to a deeper understanding of autoimmune disease molecular etiology. (frontiersin.org)

Additionally one of the proposed loci was later found to be previously reported (PARK4 and PARK1). (acnr.co.uk)

Distinguishing genetic correlation from causation across 52 diseases and complex traits. (harvard.edu)

This review summarizes and integrates research on vitamin D and CD4 + T-lymphocyte biology to develop new mechanistic insights into the molecular etiology of autoimmune disease. (frontiersin.org)
2006). The CAG repeat at the Huntington disease gene in the Portuguese population: Insights into its dynamics and to the origin of the mutation . (up.pt)
2018). Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights. (harvard.edu)

Spinal muscular atrophy (SMA) is a rare, devastating genetic disease that leads to progressive muscle weakness, paralysis, and when left untreated in one of its most severe forms (SMA Type 1), permanent ventilation or death in 90% of cases by age 2. (medicalresearch.com)

The same is also true of the most common neurodegenerative disease, Alzheimer's Disease (AD). (ukessays.com)
However, increased susceptibility to infections is common to all immunodeficiencies. (lu.se)

She established that genomic data could be adopted to decipher "signatures of natural selection and tracing mutational histories", and has used her studies to track migration patterns of many Asian populations and disease origins. (wikipedia.org)

2010). BDNF and CGRP interaction: Implications in migraine susceptibility . (up.pt)
It likely involves the interaction of host susceptibility and environmental factors. (atrainceu.com)

Advancing knowledge of human development, developmental disabilities, and neurodegenerative diseases. (wisc.edu)

Mukerji has done extensive research on hereditary ataxias, and is involved in many other projects related to tracking disease origins and mutational histories. (wikipedia.org)

Recent studies by the IGAP consortium have identified over 27 new susceptibility loci for AD. (cardiff.ac.uk)

Coronal T1-weighted magnetic resonance imaging (MRI) scan in a patient with moderate Alzheimer disease. (medscape.com)

Parkinson-plus syndromes respond poorly to the standard treatments for Parkinson disease (PD). (medscape.com)
For more information, see the Medscape Reference article Parkinson Disease. (medscape.com)

The pattern of inheritance may be elusive at times e.g. reduced penetrance associated with autosomal dominant inheritance may mimic recessive disease. (acnr.co.uk)
Both substitutions segregated with disease in agreement with a recessive pattern of inheritance within respective families and both were present as homozygous in two affected each. (biomedcentral.com)

It is an incurable disease with a long preclinical period and progressive course. (medscape.com)

Rare variation is thought to account for a proportion of the missing heritability. (neurodegenerationresearch.eu)
Thus, our C. elegans model can serve as a powerful tool to dissect the contribution of natural variation to individual susceptibility to proteotoxicity. (biomedcentral.com)
Correction: Mitochondrial DNA variation in Alzheimer's disease reveals a unique microprotein called SHMOOSE Mol Psychiatry. (usc.edu)

Anatomy26

Organisms14

Diseases57

Chemicals and Drugs57

Analytical, Diagnostic and Therapeutic Techniques and Equipment30

Psychiatry and Psychology9

Phenomena and Processes67

Disciplines and Occupations3

Information Science5

Named Groups2

Health Care8

Geographicals2

Genes24

Parkinson's Disease27

Variants18

Amyotrophic Lateral S3

GWAS3

Quantitative Trai1

Disorder3

Pathogenesis5

Genetics2

Causative2

Neurologic diseases1

Neurons3

Multiple sclerosis7

Systemic lupus erythem2

20171

Autoimmune diseases7

Clinical8

Mendelian2

Disorders3

Neurological3

Linkage2

POAG3

Sporadic6

Hypothesis1

20231

20161

Risk7

Dementia2

Functional2

Onset12

Cognitive1

Exome1

Progression3

Mutations4

Substantia nigra1

Parkinsonism1

Alzheimer's Disease Neuroimaging Initiative1

Syndrome3

Glaucoma1

Aggregation2

Patients3

Mechanisms4

Additionally1

Traits1

Insights3

Atrophy1

Common2

Genomic data1

Interaction2

Developmental1

Hereditary1

Consortium1

Alzheimer Disease1

Parkinson2

Inheritance2

Progressive1

Variation3