Abstract:
:The aim of our study was to discover genomic variations related to variant Creutzfeldt-Jakob disease (vCJD) susceptibility. A genome-wide association analysis with most vCJD samples available in the world was performed. A series of 93 vCJD UK patients and 1504 UK controls were included in the discovery stage. Our best findings were replicated in an independent population of 22 UK and 20 French vCJD cases. Post hoc analysis to assess our main results included 5711 French controls, 445 Dutch controls, and 446 sporadic Creutzfeldt-Jakob disease (CJD) cases. We found 2 genome wide significant variants tagging PRNP: rs6107516 (p = 2.6 × 10(-18)) and rs2065706 (p = 8.8 × 10(-14)). Two other single nucleotide polymorphisms (SNPs) (rs4921542 and rs7565981) were successfully replicated in independent samples and reached genome-wide significance after pooling discovery and replication populations. Rs4921542 (p = 1.6 × 10(-8)) is an intronic variant in the myotubularin related protein 7 gene (MTMR7), which is specifically expressed in the central nervous system (CNS) and dephosphorylates phosphatidylinositol 3-phosphate and inositol 1,3-bisphosphate. Rs7565981 (p = 4.2 × 10(-8)) is in an intergenic region upstream of the neuronal PAS (per-ARNT-sim) domain-containing protein 2 gene (NPAS2), a regulatory gene belonging to a family of transcription factors that has been implicated in memory, seasonal affective disorder, and the molecular clock in the mammalian forebrain. A proxy of rs7565981 (rs17024792; r(2) = 1.0) has been found to regulate the phospholipase C-delta-3 gene (PLCD3) in trans. This enzyme catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate. Our study reveals 2 new genome-wide significant markers for vCJD outside PRNP and provides evidence supporting a role of the phosphatidylinositol pathway in vCJD susceptibility.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Sanchez-Juan P,Bishop MT,Aulchenko YS,Brandel JP,Rivadeneira F,Struchalin M,Lambert JC,Amouyel P,Combarros O,Sainz J,Carracedo A,Uitterlinden AG,Hofman A,Zerr I,Kretzschmar HA,Laplanche JL,Knight RS,Will RG,van Duijndoi
10.1016/j.neurobiolaging.2011.10.011subject
Has Abstractpub_date
2012-07-01 00:00:00pages
1487.e21-8issue
7eissn
0197-4580issn
1558-1497pii
S0197-4580(11)00427-1journal_volume
33pub_type
杂志文章abstract::Hippocampal atrophy rates are useful in both diagnosing and tracking Alzheimer's disease (AD). However, cohorts and methods used to determine such rates are heterogeneous, leading to differences in reported annualised rates. We performed a meta-analysis of hippocampal atrophy rates in AD patients and matched controls ...
journal_title:Neurobiology of aging
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.neurobiolaging.2008.01.010
更新日期:2009-11-01 00:00:00
abstract::SORL1 encodes a 250-kDa protein named sorLA, a functional sorting receptor for the amyloid precursor protein (APP). Several single nucleotide polymorphisms of the gene SORL1, encoding sorLA, are genetically associated with Alzheimer's disease (AD). In the existing literature, SORL1 is insufficiently described at the t...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2018.06.021
更新日期:2018-11-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common cause of dementia and, despite decades of effort, there is no effective treatment. In the last decade, many association studies have identified genetic markers that are associated with AD status. Two of these studies suggest that an epistatic interaction between variants rs1...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2020.01.013
更新日期:2020-05-01 00:00:00
abstract::Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. ...
journal_title:Neurobiology of aging
pub_type: 杂志文章,多中心研究
doi:10.1016/j.neurobiolaging.2011.12.036
更新日期:2012-08-01 00:00:00
abstract::Somatostatin (SOM) cortical levels decline in Alzheimer's disease (AD) in correlation with cognitive impairment severity, the latter being closely related to the presence of neurofibrillary tangles. Impaired olfaction is another hallmark of AD tightly related to tau pathology in the olfactory pathways. Recent studies ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.10.033
更新日期:2015-02-01 00:00:00
abstract::Prion diseases are a diverse group of neurodegenerative conditions, caused by the templated misfolding of prion protein. Aside from the strong genetic risk conferred by multiple variants of the prion protein gene (PRNP), several other variants have been suggested to confer risk in the most common type, sporadic Creutz...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2015.01.011
更新日期:2015-05-01 00:00:00
abstract::Studies in vitro have suggested that acetylcholinesterase (AChE) may interact with beta-amyloid to promote deposition of amyloid plaques in the brain of patients with Alzheimer's disease. To test that hypothesis in vivo, we crossed Tg2576 mice, which express human amyloid precursor protein and develop plaques at 9 mon...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(02)00230-0
更新日期:2003-10-01 00:00:00
abstract::We conducted genetic analysis of the fused in sarcoma gene (FUS) in Chinese Han patients with essential tremor (ET) in a case-control association study. One hundred eighty unrelated patients with ET were screened for mutations in the coding region and exon-intron boundaries of FUS. Reverse transcriptase polymerase cha...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2013.03.001
更新日期:2013-08-01 00:00:00
abstract::Individuals with Down syndrome (DS) overexpress many genes on chromosome 21 due to trisomy and have high risk of dementia due to the Alzheimer's disease (AD) neuropathology. However, there is a wide range of phenotypic differences (e.g., age at onset of AD, amyloid β levels) among adults with DS, suggesting the import...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2017.04.018
更新日期:2017-08-01 00:00:00
abstract::Cholesterol has been implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD) and the cholesteryl ester transfer protein (CETP) is critical to cholesterol regulation within the cell, making CETP an Alzheimer's disease candidate gene. Several studies have suggested that CETP I405V (rs5882) is associated ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.08.022
更新日期:2015-01-01 00:00:00
abstract::Alzheimer's disease (AD) has been suggested to be a systemic disease, and signal transduction abnormalities have been reported in non-neuronal AD cells. We have previously quantified the protein kinase C (PKC) subtypes in AD and control brains using a two-site enzyme immunoassay (EIA), and have shown that type II PKC ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(94)90047-7
更新日期:1994-11-01 00:00:00
abstract::Long-term dietary supplementation with resveratrol protects against cardiovascular disease, osteoporesis, and metabolic decline. This study determined how long-term dietary resveratrol treatment protects against retinal ganglion cell (RGC) dendrite loss after optic nerve injury and alters the resolution of the unfolde...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.12.021
更新日期:2015-05-01 00:00:00
abstract::Genetics is intricately involved in the etiology of neurodegenerative dementias. The incidence of monogenic dementia among all neurodegenerative forms is unknown due to the lack of systematic studies and of patient/clinician access to extensive diagnostic procedures. In this study, we conducted targeted sequencing in ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2018.02.006
更新日期:2018-06-01 00:00:00
abstract::To obtain information on the mechanisms responsible of the generation of ragged red fibers (RRF) during aging, we analyzed the mitochondrial genotype of single skeletal muscle fibers of healthy individuals having an age comprised between 45 and 92 years. The sequencing of the D-loop region showed many sequence changes...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2004.06.014
更新日期:2005-05-01 00:00:00
abstract::In an autopsy series of 19 individuals, age-ranged 24-94, a relatively age-spared region, the anterior-ventral thalamus, was analyzed by immunohistochemical techniques to visualize neurons (neurofilament protein), astrocytes (glial fibrillary acidic protein), microglial cells (CD68) and amyloid precursor protein. The ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2006.12.015
更新日期:2008-06-01 00:00:00
abstract::The relationship between the neurofibrillary tangles and the intellectual deficit observed in senile dementia of the Alzheimer type was studied in 27 patients over the age of 75. The presence and density of tau positive tangles were assessed in six areas including limbic, paralimbic, and isocortical cortices. In the i...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(97)80306-5
更新日期:1997-05-01 00:00:00
abstract::Alzheimer's disease of early onset versus that of late onset represent different syndromes, with distinct neuropathologies. Patients with early onset disease exhibit a more severe and more widespread loss of neurons from cortical and sub-cortical regions and the neurochemical changes involve not only the cholinergic s...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(87)90132-1
更新日期:1987-11-01 00:00:00
abstract::It was previously reported that in soleus neuromuscular junctions of old mice, synaptic vesicle density was decreased while transmitter release was increased (compared to results in young mice). In the present study, two hypotheses that might resolve this disparity were tested. The first was that the density of readil...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(87)90061-3
更新日期:1987-01-01 00:00:00
abstract::Healthy aging is associated with declines in episodic memory performance that are due in part to deficits in encoding. Emerging results from young adult studies suggest that the neural activity during the time preceding stimulus presentation is sensitive to episodic memory performance. It is unknown whether age-relate...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2019.01.005
更新日期:2019-05-01 00:00:00
abstract::Abnormal elevations in ammonia have been implicated in the pathogenesis of Alzheimer's disease. However, the biochemical mechanism(s) leading to increased ammonia in Alzheimer's disease have not yet been identified. A potential source of increased ammonia production is adenosine monophosphate (AMP) deaminase, an impor...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(98)00083-9
更新日期:1998-09-01 00:00:00
abstract::Striatal degeneration may contribute to cognitive impairment in older people. Here, we examine the relation of degeneration of the striatum and substructures to cognitive decline and dementia in subjects with a wide range of cognitive function. Data are from the prospective community-based Honolulu Asia Aging Study of...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2010.09.027
更新日期:2012-02-01 00:00:00
abstract::The C9orf72 expansion is considered a major genetic cause of familial frontotemporal dementia (FTD) in several patients' cohorts. Interestingly, C9orf72 expansion carriers, present also abundant neuronal p62-positive inclusions. Although p62/SQSTM1 mutations were initially associated with Paget disease of bone (PDB), ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2015.12.015
更新日期:2016-04-01 00:00:00
abstract::Neurofibrillary degeneration in the nucleus basalis and a loss of its cortical cholinergic projections are prominent components of the neuropathology in Alzheimer's disease (AD). The AD brain is also associated with a degeneration of the noradrenergic projections arising from the nucleus locus coeruleus (LC), but the ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2006.02.007
更新日期:2007-03-01 00:00:00
abstract::A group of 51 healthy elderly volunteer subjects participated in a 3- to 6-year longitudinal study of basal cortisol levels. Once per year basal cortisol levels were examined using hourly sampling over a 24-h period. Analyses of three cortisol measures (last measure obtained, mean cortisol levels across years, and the...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(95)02005-5
更新日期:1996-01-01 00:00:00
abstract::We previously established a single-neuron culture system to analyze the primary effects of neurotrophic factors and reported that NGF promoted neurite extension in young adult (4- to 6-month-old) rat dorsal root ganglion (DRG) neurons by promoting neurite arborization. In this study, we demonstrated that the effects o...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(93)90093-q
更新日期:1993-03-01 00:00:00
abstract::Multiple degenerative hallmarks characterize Alzheimer's disease: insoluble protein deposition, neuronal loss and cortical atrophy. Atrophy begins in the medial temporal lobe and becomes global by end stage. In a small proportion of cases, these tissue changes are caused by mutations in three known genes. These cases ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2005.03.011
更新日期:2006-03-01 00:00:00
abstract::The first hypothesis free genome wide association study on cognition recently revealed the thus far unknown association of a single nucleotide polymorphism (SNP) of the KIBRA gene with episodic memory in healthy young and middle aged volunteers. Here, we report the first independent replication of this finding in an i...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2007.02.001
更新日期:2008-07-01 00:00:00
abstract::Cluster of Differentiation-200 (CD200) is an anti-inflammatory glycoprotein expressed in neurons, T cells, and B cells, and its receptor is expressed on glia. Both Alzheimer's disease patients and mouse models display age-related or amyloid-β peptide (Aβ)-induced reductions in CD200. The goal of this study was to dete...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2015.07.027
更新日期:2015-11-01 00:00:00
abstract::We have assessed the frequency of alpha-synuclein (SNCA) mutations in Japanese patients with familial or sporadic Parkinson's disease (PD) and surveyed their associated clinical manifestations. We screened SNCA exon 3 in 988 patients without SNCA multiplications (430 with autosomal dominant PD and 558 with sporadic PD...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2017.05.022
更新日期:2017-09-01 00:00:00
abstract::Genome-wide association studies have associated clusterin (CLU) variants with Alzheimer's disease (AD). However, the role of CLU on AD pathogenesis is not totally understood. We used cerebrospinal fluid (CSF) and plasma CLU levels as endophenotypes for genetic studies to understand the role of CLU in AD. CSF, but not ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2015.09.009
更新日期:2016-01-01 00:00:00