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Epidemiological and clinical trials evidence about a preventive role for statins in Alzheimer's disease.关于他汀类药物在阿尔茨海默病预防作用的流行病学和临床试验证据。
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Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism.载脂蛋白E ε4基因剂量与区域代谢减退的脑成像测量之间的相关性。
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胆固醇相关的遗传风险评分与阿尔茨海默病受累脑区的代谢减退有关。

Cholesterol-related genetic risk scores are associated with hypometabolism in Alzheimer's-affected brain regions.

作者信息

Reiman Eric M, Chen Kewei, Caselli Richard J, Alexander Gene E, Bandy Daniel, Adamson Jennifer L, Lee Wendy, Cannon Ashley, Stephan Elizabeth A, Stephan Dietrich A, Papassotiropoulos Andreas

机构信息

Banner Alzheimer's Institute and Banner Good Samaritan PET Center, Phoenix, AZ 85006, USA.

出版信息

Neuroimage. 2008 Apr 15;40(3):1214-21. doi: 10.1016/j.neuroimage.2007.12.066. Epub 2008 Jan 17.

DOI:10.1016/j.neuroimage.2007.12.066
PMID:18280754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2441925/
Abstract

We recently implicated a cluster of nine single nucleotide polymorphisms from seven cholesterol-related genes in the risk of Alzheimer's disease (AD) in a European cohort, and we proposed calculating an aggregate cholesterol-related genetic score (CREGS) to characterize a person's risk. In a separate study, we found that apolipoprotein E (APOE) epsilon4 gene dose, an established AD risk factor, was correlated with fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements of hypometabolism in AD-affected brain regions in a cognitively normal American cohort, and we proposed using PET as a presymptomatic endophenotype to help assess putative modifiers of AD risk. Thus, the objective in the present study is to determine whether CREGS is related to PET measurements of hypometabolism in AD-affected brain regions. DNA and PET data from 141 cognitively normal late middle-aged APOE epsilon4 homozygotes, heterozygotes and noncarriers were analyzed to evaluate the relationship between CREGS and regional PET measurements. Cholesterol-related genetic risk scores were associated with hypometabolism in AD-affected brain regions, even when controlling for the effects of APOE epsilon4 gene dose. The results support the role of cholesterol-related genes in the predisposition to AD and support the value of neuroimaging in the presymptomatic assessment of putative modifiers of AD risk.

摘要

我们最近在一个欧洲队列中发现，来自7个胆固醇相关基因的9个单核苷酸多态性与阿尔茨海默病（AD）风险相关，并且我们提议计算一个综合胆固醇相关基因评分（CREGS）来表征一个人的风险。在另一项研究中，我们发现载脂蛋白E（APOE）ε4基因剂量（一种已确定的AD风险因素）与认知正常的美国队列中AD受累脑区低代谢的氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）测量结果相关，并且我们提议使用PET作为症状前内表型来帮助评估AD风险的假定修饰因子。因此，本研究的目的是确定CREGS是否与AD受累脑区低代谢的PET测量结果相关。分析了141名认知正常的中老年APOE ε4纯合子、杂合子和非携带者的DNA和PET数据，以评估CREGS与PET区域测量结果之间的关系。即使在控制了APOE ε4基因剂量的影响后，胆固醇相关基因风险评分仍与AD受累脑区的低代谢相关。这些结果支持胆固醇相关基因在AD易感性中的作用，并支持神经影像学在AD风险假定修饰因子的症状前评估中的价值。