Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment
Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment
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DOI：
10.1016/j.jalz.2016.01.006
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发表时间：
2016-08-01
影响因子：
14
通讯作者：
Ramirez, Alfredo
中科院分区：
文献类型：
--
作者：
Louwersheimer, Eva;Wolfsgruber, Steffen;Ramirez, Alfredo
前言：我们研究了阿尔茨海默病(AD)易感基因座对轻度认知障碍(MCI)患者与AD病理密切相关的内表型的影响。对18个非载脂蛋白E(APOE)AD风险变异体构建加权多基因风险评分(PGS)。此外，我们还进行了APOE基因分型。AD内表型为认知功能减退和脑脊液(CSF)生物标志物(aβ、tau、ptau)。结果：简易智力状态检查(MMSE)显示PGS与认知功能减退有一定的相关性(β+/-SE：0.24+/-0.10；P=0.012)，与脑脊液tau和ptau水平(tau：1.38+/-0.36，P=1.21×10(-4))相关；Ptau：1.40+/-0.36，P=1.02×10(-4)。讨论：在MCI中，我们观察到AD易感基因座对非淀粉样内表型的联合影响，提示这些遗传位点与神经元变性有关，而不是与阿尔茨海默病相关的淀粉样蛋白沉积有关。(C)2016年阿尔茨海默氏症协会。爱思唯尔公司出版，版权所有。
Introduction: We evaluated the effect of Alzheimer's disease (AD) susceptibility loci on endophenotypes closely related with AD pathology in patients with mild cognitive impairment (MCI).Methods: We selected 1730 MCI patients from four independent data sets. Weighted polygenic risk scores (PGS) were constructed of 18 non-apolipoprotein E (APOE) AD risk variants. In addition, we determined APOE genotype. AD endophenotypes were cognitive decline over time and cerebrospinal fluid (CSF) biomarkers (a beta, tau, ptau).Results: PGS was modestly associated with cognitive decline over time, as measured by mini-mental state examination (MMSE) (beta +/- SE: 0.24 +/- 0.10; P = .012), and with CSF levels of tau and ptau (tau: 1.38 +/- 0.36, P = 1.21 x 10(-4); ptau: 1.40 +/- 0.36, P = 1.02 x 10(-4)).Discussion: In MCI, we observed a joint effect of AD susceptibility loci on nonamyloid endophenotypes, suggesting a link of these genetic loci with neuronal degeneration in general rather than with Alzheimer-related amyloid deposition. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.