The Effects of rs405509 on APOEε4 Non-carriers in Non-demented Aging.

Dongpeng Wu,Jinping Sun,Xu Man,Xuejun Liu,Renliang Zhao,Qingqing Wang,Han Zhao,Bin Han,Huali Gu

doi:10.3389/fnins.2021.677823

Abstract

BackgroundThere is evidence that the T allele of rs405509 located in the apolipoprotein E (APOE) promotor region is a risk factor for Alzheimer’s disease (AD). However, the effect of the T/T allele on brain function in non-demented aging is still unclear.MethodsWe analyzed the effects of the rs405509 T/T allele on cognitive performances using multiple neuropsychological tests and local brain function using resting-state functional magnetic resonance imaging (rs-fMRI).ResultsSignificant differences were found between T/T carriers and G allele carriers on general cognitive status, memory, and attention (p < 0.05). Rs-fMRI analyses demonstrated decreased amplitude of low frequency fluctuation (ALFF) in the right middle frontal gyrus, decreased percent amplitude of fluctuation (PerAF) in the right middle frontal gyrus, increased regional homogeneity (ReHo) in the right cerebellar tonsil and decreased ReHo in the right putamen, and decreased degree centrality (DC) in the left middle frontal gyrus (p < 0.05, corrected). Furthermore, significant correlations were found between cognitive performance and these neuroimaging changes (p < 0.05).ConclusionThese findings suggest that T/T allele may serve as an independent risk factor that can influence brain function in different regions in non-demented aging.

Highlights

Alzheimer’s disease (AD) is a degenerative disease of the brain characterized by progressive cognitive and behavioral impairment in the elderly and the early stages of old age (Ferri et al, 2005)
We aimed to determine whether and how rs405509 influences the local function using distinct imaging metrics (ReHo, amplitude of low frequency fluctuation (ALFF), Fractional amplitude of low frequency fluctuations (fALFF), percent amplitude of fluctuation (PerAF), and degree centrality (DC)) and whether these local alterations would be related to the clinical features of the participants
The results showed that compared with the G allele carriers, the T/T carriers manifested decreased ALFF in the right middle frontal gyrus, decreased PerAF in the right middle frontal gyrus, increased regional homogeneity (ReHo) in the right cerebellum posterior lobe, decreased ReHo in the right putamen, and decreased DC in the left middle frontal gyrus

Summary

Introduction

Alzheimer’s disease (AD) is a degenerative disease of the brain characterized by progressive cognitive and behavioral impairment in the elderly and the early stages of old age (Ferri et al, 2005). Compared with non-carriers, carriers of the ε4 allele of the APOE gene have been shown to be associated with a higher risk of developing Alzheimer’s disease in late-onset families (van der Flier et al, 2011). The rs405509 According to previous reports, the APOE promotor’s T/T allele is a verisimilar risk factor for developing AD (Beyer et al, 2002). This polymorphism is associated with myocardial infarction and has become a common risk factor for cardiovascular disease and neurodegenerative disease, in aging (Lambert et al, 2000; Ye et al, 2003). There is evidence that the T allele of rs405509 located in the apolipoprotein E (APOE) promotor region is a risk factor for Alzheimer’s disease (AD). The effect of the T/T allele on brain function in non-demented aging is still unclear

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