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 importance of factors that modify risk within this particularly vulnerable population, including genotypic variability. Previous genetic studies in the general population have identified multiple genes that are associated with AD. This study examined the contribution of polymorphisms in these genes to the risk of AD in adults with DS ranging from 30 to 78 years of age at study entry (N = 320). We used multiple logistic regressions to estimate the likelihood of AD using single-nucleotide polymorphisms (SNPs) in candidate genes, adjusting for age, sex, race/ethnicity, level of intellectual disability and APOE genotype. This study identified multiple SNPs in APP and CST3 that were associated with AD at a gene-wise level empirical p-value of 0.05, with odds ratios in the range of 1.5-2. SNPs in MARK4 were marginally associated with AD. CST3 and MARK4 may contribute to our understanding of potential mechanisms where CST3 may contribute to the amyloid pathway by inhibiting plaque formation, and MARK4 may contribute to the regulation of the transition between stable and dynamic microtubules.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Lee JH,Lee AJ,Dang LH,Pang D,Kisselev S,Krinsky-McHale SJ,Zigman WB,Luchsinger JA,Silverman W,Tycko B,Clark LN,Schupf Ndoi
10.1016/j.neurobiolaging.2017.04.018subject
Has Abstractpub_date
2017-08-01 00:00:00pages
150-158eissn
0197-4580issn
1558-1497pii
S0197-4580(17)30146-Xjournal_volume
56pub_type
杂志文章abstract：:Brains were examined from 22 patients with Alzheimer's disease (AD) (mean age 80.5, S.D. 11.5) and were compared with brains from 20 nondiseased subjects (mean age 81.1, S.D. 10.2). Intraneuronal lipopigment in all layers of a region of the superior frontal cortex was identified by fluorescence microscopy. The areas e...
journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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journal_title：Neurobiology of aging
pub_type： 杂志文章,meta分析
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更新日期：2020-02-01 00:00:00
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journal_title：Neurobiology of aging
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pub_type： 杂志文章
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.07.002
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.07.003
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.07.016
更新日期：2011-03-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.10.017
更新日期：2011-10-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.10.007
更新日期：2013-04-01 00:00:00
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
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pub_type： 杂志文章
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更新日期：2016-04-01 00:00:00
abstract：:Individuals with Down syndrome (DS), caused by trisomy of chromosome 21, inevitably develop characteristic Alzheimer's disease (AD) neuropathology, including neuritic plaques, neurofibrillary tangles, and neuronal loss. Amyloid-β protein, the major component of neuritic plaques, is the proteolytic product of amyloid-β...
journal_title：Neurobiology of aging
pub_type： 杂志文章
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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abstract：:Alzheimer's disease (AD) pathology has been described in Parkinson's disease (PD) patients with leucine-rich repeat kinase-2 (LRRK2) mutations. A common LRRK2 Gly2385Arg variant has been widely shown to be associated with a twofold increased risk of PD in various Asian populations. In a case control study, the frequen...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.07.010
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abstract：:Iron overload may contribute to the risk of Alzheimer's disease (AD). In the Epistasis Project, with 1757 cases of AD and 6295 controls, we studied 4 variants in 2 genes of iron metabolism: hemochromatosis (HFE) C282Y and H63D, and transferrin (TF) C2 and -2G/A. We replicated the reported interaction between HFE 282Y ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
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