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正常衰老过程中的定量脑电图:与PICALM基因中阿尔茨海默病遗传风险变异的关联

Quantitative EEG during normal aging: association with the Alzheimer's disease genetic risk variant in PICALM gene.

作者信息

Ponomareva Natalya V, Andreeva Tatiana V, Protasova Maria S, Shagam Lef I, Malina Daria D, Goltsov Andrey Yu, Fokin Vitaly F, Illarioshkin Sergey N, Rogaev Evgeny I

机构信息

Research Center of Neurology, Moscow, Russia; Vavilov Institute of General Genetics, RAS, Moscow, Russia.

Vavilov Institute of General Genetics, RAS, Moscow, Russia; Center of Brain Neurobiology and Neurogenetics, Institute of Cytogenetics and Genetics RAMS, Novosibirsk, Russia.

出版信息

Neurobiol Aging. 2017 Mar;51:177.e1-177.e8. doi: 10.1016/j.neurobiolaging.2016.12.010. Epub 2016 Dec 20.

Abstract

Genome-wide association studies have identified novel risk variants for Alzheimer's disease (AD). Among these, a gene carrying one of the highest risks for AD is PICALM. The PICALM rs3851179 A allele is thought to have a protective effect, whereas the G allele appears to confer risk for AD. The influence of the PICALM genotype on brain function in nondemented subjects remains largely unknown. We examined the possible effect of the PICALM rs3851179 genotype on quantitative electroencephalography recording at rest in 137 nondemented volunteers (age range: 20-79 years) subdivided into cohorts of those younger than and those older than 50 years of age. The homozygous presence of the AD risk variant PICALM GG was associated with an increase in beta relative power, with the effect being more pronounced in the older cohort. Beta power elevation in resting-state electroencephalography has previously been linked to cortical disinhibition and hyperexcitability. The increase in beta relative power in the carriers of the AD risk PICALM GG genotype suggests changes in the cortical excitatory-inhibitory balance, which are heightened during normal aging.

摘要

全基因组关联研究已经确定了阿尔茨海默病(AD)的新型风险变异。其中,携带AD最高风险之一的基因是PICALM。PICALM rs3851179 A等位基因被认为具有保护作用,而G等位基因似乎会增加患AD的风险。PICALM基因型对非痴呆受试者脑功能的影响在很大程度上仍然未知。我们在137名非痴呆志愿者(年龄范围:20 - 79岁)中,研究了PICALM rs3851179基因型对静息状态下定量脑电图记录的可能影响,这些志愿者被分为年龄小于50岁和大于50岁的队列。AD风险变异PICALM GG的纯合存在与β相对功率增加有关,这种影响在老年队列中更为明显。静息状态脑电图中的β功率升高此前已与皮质去抑制和过度兴奋有关。AD风险PICALM GG基因型携带者中β相对功率的增加表明皮质兴奋 - 抑制平衡发生了变化,这种变化在正常衰老过程中会加剧。

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