基于神经病理学的 APOE 遗传风险评分能更好地量化阿尔茨海默病风险。
Neuropathology-based APOE genetic risk score better quantifies Alzheimer's risk.
机构信息
Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
出版信息
Alzheimers Dement. 2023 Aug;19(8):3406-3416. doi: 10.1002/alz.12990. Epub 2023 Feb 16.
INTRODUCTION
Apolipoprotein E (APOE) ε4-carrier status or ε4 allele count are included in analyses to account for the APOE genetic effect on Alzheimer's disease (AD); however, this does not account for protective effects of APOE ε2 or heterogeneous effect of ε2, ε3, and ε4 haplotypes.
METHODS
We leveraged results from an autopsy-confirmed AD study to generate a weighted risk score for APOE (APOE-npscore). We regressed cerebrospinal fluid (CSF) amyloid and tau biomarkers on APOE variables from the Wisconsin Registry for Alzheimer's Prevention (WRAP), Wisconsin Alzheimer's Disease Research Center (WADRC), and Alzheimer's Disease Neuroimaging Initiative (ADNI).
RESULTS
The APOE-npscore explained more variance and provided a better model fit for all three CSF measures than APOE ε4-carrier status and ε4 allele count. These findings were replicated in ADNI and observed in subsets of cognitively unimpaired (CU) participants.
DISCUSSION
The APOE-npscore reflects the genetic effect on neuropathology and provides an improved method to account for APOE in AD-related analyses.
简介
载脂蛋白 E (APOE) ε4 携带者状态或 ε4 等位基因数被纳入分析，以解释 APOE 基因对阿尔茨海默病 (AD) 的影响；然而，这并没有考虑到 APOE ε2 的保护作用或 ε2、ε3 和 ε4 单倍型的异质性影响。
方法
我们利用经尸检证实的 AD 研究的结果，生成了载脂蛋白 E 的加权风险评分（APOE-npscore）。我们将脑脊液 (CSF) 淀粉样蛋白和 tau 生物标志物与威斯康星州阿尔茨海默病预防注册中心 (WRAP)、威斯康星州阿尔茨海默病研究中心 (WADRC) 和阿尔茨海默病神经影像学倡议 (ADNI) 的 APOE 变量进行回归。
结果
APOE-npscore 比 APOE ε4 携带者状态和 ε4 等位基因数更好地解释了所有三种 CSF 指标的变异性，并提供了更好的模型拟合。这些发现在 ADNI 中得到了复制，并在认知正常 (CU) 参与者的亚组中观察到。
讨论
APOE-npscore 反映了基因对神经病理学的影响，并为 AD 相关分析中考虑 APOE 提供了一种改进的方法。
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