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Effect of PICALM rs3851179 polymorphism on the default mode network function in mild cognitive impairment.

Abstract：

:Alterations in default mode network (DMN) functional connectivity (FC) might accompany the dysfunction of Alzheimer's disease (AD). Indeed, episodic memory impairment is a hallmark of AD, and mild cognitive impairment (MCI) has been associated with a high risk for AD. Phosphatidylinositol-binding clathrin assembly protein (PICALM) (rs3851179) has been associated with AD; in particular, the A allele may serve a protective role, while the G allele serves as a strong genetic risk factor. Therefore, the identification of genetic polymorphisms associated with the DMN is required in MCI subjects. In all, 32 MCI subjects and 32 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) and a genetic imaging approach. Subjects were divided into four groups according to the diagnosis (i.e., MCI and HCs) and the PICALM rs3851179 polymorphism (i.e., AA/AG genotype and GG genotype). The differences in FC within the DMN between the four subgroups were explored. Furthermore, we examined the relationship between our neuroimaging measures and cognitive performance. The regions associated with the genotype-by-disease interaction were in the left middle temporal gyrus (LMTG) and left middle frontal gyrus (LMFG). These changes in LMFG FC were generally manifested as an "inverse U-shaped curve", while a "U-shaped curve" was associated with the LMTG FC between these four subgroups (all P<0.05). Furthermore, higher FC within the LMFG was related to better episodic memory performance (i.e., AVLT 20min DR, rho=0.72, P=0.044) for the MCI subgroups with the GG genotype. The PICALM rs3851179 polymorphism significantly affects the DMN network in MCI. The LMFG and LMTG may be associated with opposite patterns. However, the altered LMFG FC in MCI patients with the GG genotype was more sensitive to episodic memory impairment, which is more likely to lead to a high risk of AD.

journal_name

Behav Brain Res

journal_title

Behavioural brain research

authors

Sun DM,Chen HF,Zuo QL,Su F,Bai F,Liu CF

doi

10.1016/j.bbr.2017.05.043

subject

Has Abstract

pub_date

2017-07-28 00:00:00

pages

225-232

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(17)30027-X

journal_volume

331

pub_type

杂志文章

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Effect of PICALM rs3851179 polymorphism on the default mode network function in mild cognitive impairment.