Research Papers: Gerotarget (Focus on Aging):

Multiple genetic imaging study of the association between cholesterol metabolism and brain functional alterations in individuals with risk factors for Alzheimer’s disease

Feng Bai _, Yonggui Yuan, Yongmei Shi and Zhijun Zhang

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Oncotarget. 2016; 7:15315-15328. https://doi.org/10.18632/oncotarget.8100

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Feng Bai1, Yonggui Yuan1, Yongmei Shi1 and Zhijun Zhang1

1 Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China

Correspondence to:

Zhijun Zhang, email:

Feng Bai, email:

Keywords: cholesterol metabolism pathway, imaging genetics, brain function, amnestic mild cognitive impairment, Alzheimer’s disease, Gerotarget

Received: January 14, 2016 Accepted: February 28, 2016 Published: March 15, 2016


Alzheimer’s disease (AD) is a clinically and genetically heterogeneous neurodegenerative disease. Genes involved in cholesterol metabolism may play a role in the pathological changes of AD. However, the imaging genetics-based endophenotypes derived from polymorphisms in multiple functionally related genes are unclear in individuals with risk factors for AD. Forty-three amnestic mild cognitive impairment (aMCI) subjects and 30 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) measurements of brain topological organization. Thirty-three previously suggested tagging single nucleotide polymorphisms (SNPs) from 12 candidate genes in the cholesterol metabolism pathway were further investigated. A cholesterol metabolism pathway gene-based imaging genetics approach was then utilized to investigate disease-related differences between the groups based on genotype-by-aMCI interactions. The cholesterol metabolism pathway genes exerted widespread effects on the cortico-subcortical-cerebellar spontaneous brain activity. Meanwhile, left lateralization of global brain connectivity was associated with cholesterol metabolism pathway genes. The APOE rs429358 variation significantly influenced the brain network characteristics, affecting the activation of nodes as well as the connectivity of edges in aMCI subjects.The cholesterol metabolism pathway gene-based imaging genetics approach may provide new opportunities to understand the mechanisms underlying AD and suggested that APOE rs429358 is a core genetic variation that is associated with disease-related differences in brain function.

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