期刊
BRAIN PATHOLOGY
卷 22, 期 6, 页码 765-775出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1750-3639.2012.00586.x
关键词
Alzheimer's disease; neurofibrillary tangles; senile plaques; upstream transcription factor 1
资金
- Medical Research Fund of Tampere University Hospital
- Pirkanmaa Regional Fund of the Finnish Cultural Foundation
- Finnish Foundation for Cardiovascular Research
The apolipoprotein E (APOE) gene associates with Alzheimer's disease (AD) and cholesterol levels. Upstream transcription factor 1 (USF1) regulates lipid metabolism genes, including APOE, and the AD A beta-precursor protein. We investigated associations between 6 haplotype-tagging USF1 single-nucleotide polymorphisms (and haplotypes) and AD-related neuropathological lesions [senile plaques (SP), neurofibrillary tangles (NFT) ] in an autopsy series comprising 603 cases (ages 097, mean 62 years, 215 women) that died out-of-hospital. In age- and APOE-adjusted analyses, the minor G-allele of rs2774276, previously linked to elevated cholesterol, associated with late-stage burnt out SP among women and early non-neuritic SP among men. The G-allele of the previously unreported rs10908821 showed significant risk of having SP, especially neuritic and burnt out SP, among women but not men. USF1 haplotype GCGCAC carriers (risk alleles of rs2774276 and rs10908821) associated with SP risk, especially neuritic and late-stage burnt out SP, among women but not men. Younger CCGCAC carriers (risk allele of rs2774276 and protective of rs10908821) were more likely to have non-neuritic and diffuse SP. Conversely, USF1 CCGCAC haplotype carriers had lower NFT prevalence among 65+ year-olds. These results suggest USF1 has an independent but gender- and age-associated effect on AD-related brain lesion development.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据