载脂蛋白 E 和儿茶酚-O-甲基转移酶基因多态性是正常衰老和早期轻度认知障碍的状态、稳定性和转变的互补生物标志物。

APOE and COMT polymorphisms are complementary biomarkers of status, stability, and transitions in normal aging and early mild cognitive impairment.

机构信息

Department of Psychology, University of Alberta Edmonton, AB, Canada ; Neuroscience and Mental Health Institute, University of Alberta Edmonton, AB, Canada.

Department of Psychology, University of Victoria Victoria, BC, Canada.

出版信息

Front Aging Neurosci. 2014 Sep 5;6:236. doi: 10.3389/fnagi.2014.00236. eCollection 2014.

DOI:10.3389/fnagi.2014.00236

PMID:25249975

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4155788/

Abstract

OBJECTIVE

Research has reported associations among selected genetic susceptibility biomarkers and risk of (a) normal cognitive aging decrements, (b) established mild cognitive impairment (MCI), and (c) sporadic Alzheimer's disease (AD). In focusing on the transitional normal-to-early MCI phase, we examine associations among three theoretically relevant polymorphisms (APOE [rs429358, rs7412], BDNF [rs6265], COMT [rs4680]) and both baseline cognitive status (MCI vs. normal aging) and two-wave (four-year) longitudinal stability or change profiles. The latter included three profiles: (a) stable as normal aging, (b) stable or chronic impairment (MCI-to-MCI), and (c) emergence of impairment (normal-to-MCI).

METHOD

Genotyped older adults (n = 237 at baseline; age range = 64-91; 62% women) from the Victoria Longitudinal Study were examined for (a) independent and interactive associations of three genetic polymorphisms with (b) two objectively classified cognitive status groups (not-impaired controls (NIC) and MCI) at (c) both baseline and across a two-wave (four-year) longitudinal interval.

RESULTS

First, logistic regression revealed that the presence of at least one APOE ε4 allele (the risk factor for AD) was linked to greater baseline risk of objective MCI. Second, multinomial logistic regression revealed that (a) the presence of an APOE ε4 allele was associated with an increased risk of 4-year MCI status stability (chronicity), and (b) the COMT homozygous risk genotype (G/G or Val/Val) was associated with an increased risk of both MCI-to-MCI stability (chronicity) and emerging NIC-to-MCI conversion.

DISCUSSION

Both chronicity and emergence of objectively classified early cognitive impairment may be genetically heterogeneous phenomena, with influences from a panel of both normal cognitive aging (COMT) and AD-related (APOE) polymorphisms.

摘要

目的

研究报告了一些遗传易感性生物标志物与（a）正常认知衰老衰退、（b）已确立的轻度认知障碍（MCI）和（c）散发性阿尔茨海默病（AD）的风险之间的关联。在关注从正常向早期 MCI 过渡的阶段，我们研究了三个理论上相关的多态性（APOE [rs429358，rs7412]、BDNF [rs6265]、COMT [rs4680]）与基线认知状态（MCI 与正常衰老）和两波（四年）纵向稳定性或变化谱之间的关联。后者包括三种情况：（a）稳定为正常衰老，（b）稳定或慢性损害（MCI 到 MCI），和（c）出现损害（正常到 MCI）。

方法

对维多利亚纵向研究中的老年被试（基线时 237 名；年龄范围 64-91 岁；62%为女性）进行基因分型，以检查（a）三个基因多态性与（b）两个客观分类的认知状态组（未受损对照组（NIC）和 MCI）之间的（c）独立和交互关联，以及在（c）两波（四年）纵向间隔内。

结果

首先，逻辑回归显示，至少携带一个 APOE ε4 等位基因（AD 的风险因素）与更大的基线客观 MCI 风险相关。其次，多项逻辑回归显示，（a）APOE ε4 等位基因的存在与 4 年 MCI 状态稳定性（慢性）的风险增加有关，以及（b）COMT 纯合风险基因型（G/G 或 Val/Val）与 MCI 到 MCI 稳定性（慢性）和新出现的 NIC 到 MCI 转换的风险增加有关。