载脂蛋白 E ε2 等位基因对认知正常个体灰质体积的保护基因剂量效应。
The protective gene dose effect of the APOE ε2 allele on gray matter volume in cognitively unimpaired individuals.
机构信息
Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
出版信息
Alzheimers Dement. 2022 Jul;18(7):1383-1395. doi: 10.1002/alz.12487. Epub 2021 Dec 8.
INTRODUCTION
Harboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described.
METHODS
Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of ε2 genotypic groups were compared to each other and to the reference group (APOE ε3/ε3).
RESULTS
Carrying at least one ε2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE ε2 homozygotes, but not APOE ε2 heterozygotes, showed larger GM volumes in areas related to successful aging.
DISCUSSION
In addition to the known resistance against amyloid-β deposition, the larger GM volumes in key brain regions may confer APOE ε2 homozygotes additional protection against AD-related cognitive decline.
简介
携带两份载脂蛋白 E（APOE）ε2 等位基因强烈保护个体免受阿尔茨海默病（AD）的影响。然而，这种基因型对认知正常个体的灰质（GM）体积的影响尚未被描述。
方法
对认知正常的 ε2 纯合子进行多中心脑磁共振成像（MRI），并根据相关混杂因素（n=223）与所有其他 APOE 基因型进行匹配（1:1）。比较 ε2 基因型组的 GM 体积与彼此以及与参考组（APOE ε3/ε3）。
结果
携带至少一个 ε2 等位基因与 AD 常见受累脑区以及与认知弹性相关的脑区的 GM 体积增加有关。APOE ε2 纯合子，而不是 APOE ε2 杂合子，在与成功老化相关的区域显示出更大的 GM 体积。
讨论
除了已知的对淀粉样蛋白-β沉积的抵抗作用外，关键脑区的更大 GM 体积可能使 APOE ε2 纯合子对 AD 相关的认知下降提供额外的保护。
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