Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Department of Neurology, Duke University School of Medicine, Durham, NC, USA.
Alzheimers Dement. 2017 Dec;13(12):1380-1388. doi: 10.1016/j.jalz.2017.05.002. Epub 2017 Jun 15.
The study investigated the role of neuropathologies in the relationship between TOMM40 '523 genotype and late-life cognitive decline.
Participants were community-dwelling older persons who had annual cognitive assessments and brain autopsies after death. Genotyping used DNA from peripheral blood or postmortem brain tissue. Linear mixed models assessed the extent to which the association of '523 genotype with cognitive decline is attributable to neuropathologies.
Relative to ε3/ε3 homozygotes with '523-S/VL or '523-VL/VL genotype, both '523-L carriers and ε3/ε3 homozygotes with '523-S/S genotype had faster cognitive decline. The association of '523-L with cognitive decline was attenuated and no longer significant after controlling for Alzheimer's and other neuropathologies. By contrast, the association of '523-S/S was unchanged.
There are two distinct TOMM40 '523 signals in relation to late-life cognitive decline. One signal primarily acts through AD and other common neuropathologies, whereas the other operates through a different mechanism.
本研究调查了神经病理学在 TOMM40 '523 基因型与晚年认知衰退之间关系中的作用。
参与者为居住在社区的老年人，他们在死亡后每年进行认知评估和大脑尸检。基因分型使用外周血或死后脑组织中的 DNA 进行。线性混合模型评估了 '523 基因型与认知衰退之间的关联在多大程度上归因于神经病理学。
与 '523-S/VL 或 '523-VL/VL 基因型的 ε3/ε3 纯合子相比，'523-L 携带者和 '523-S/S 基因型的 ε3/ε3 纯合子的认知衰退速度更快。在控制阿尔茨海默病和其他神经病理学之后，'523-L 与认知衰退的关联减弱且不再显著。相比之下，'523-S/S 的关联保持不变。
与晚年认知衰退相关的 TOMM40 '523 存在两种截然不同的信号。一个信号主要通过 AD 和其他常见神经病理学起作用，而另一个则通过不同的机制起作用。
