Genetic Variants of PICALM rs541458 Modulate Brain Spontaneous Activity in Older Adults With Amnestic Mild Cognitive Impairment.

Abstract:

:Background: Phosphatidylinositol binding clathrin assembly protein (PICALM) rs541458 C allele has been identified and validated to be associated with a reduction of Alzheimer's disease (AD) risk. Nevertheless, the exact mechanisms through which the variant exert its disease-relevant association remain to be elucidated. This study is to determine whether PICALM rs541458 polymorphism modulates functional magnetic resonance imaging measured brain spontaneous activity in older adults with amnestic mild cognitive impairment (aMCI). Methods: Thirty five aMCI patients and twenty six healthy controls (HC) were enrolled in this study. Each individual was genotyped for rs541458 and scanned with resting-state functional magnetic resonance imaging. Each group was divided into two subgroups (C carriers and TT genotype). Brain activity was measured with amplitude of low-frequency fluctuation (ALFF). Results: The aMCI patients showed decreased ALFF in left inferior frontal gyrus, superior temporal gyrus and insula, while increased ALFF in right cuneus, calcarine, and bilateral posterior cingulate and precuneus. A significant interaction between diagnosis (aMCI vs. HC) and PICALM rs541458 genotype (C carriers vs. TT) on ALFF was observed mainly in the right frontal lobe, with aMCI C carriers and TT genotype in HC showing significantly lower ALFF than HC C carriers. While only negative correlation between ALFF and verbal fluency test was found in HC C carriers (r = -0.543, p = 0.030). Conclusions: This study provided preliminary evidences that PICALM rs541458 variations may modulate the spontaneous brain activity in aMCI patients.

journal_name

Front Neurol

journal_title

Frontiers in neurology

authors

Zhuang L,Liu X,Shi Y,Liu X,Luo B

doi

10.3389/fneur.2019.00494

subject

Has Abstract

pub_date

2019-05-08 00:00:00

pages

494

issn

1664-2295

journal_volume

10

pub_type

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