title: Multiple genetic imaging study of the association between cholesterol metabolism and brain functional alterations in individuals with risk factors for Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Bai
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Yonggui
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C000612345:ApoE protein, human; D001057:Apolipoproteins E; D002784:Cholesterol
keywords: Alzheimer’s disease; Gerotarget; amnestic mild cognitive impairment; brain function; cholesterol metabolism pathway; imaging genetics