title: Immunity factor contributes to altered brain functional networks in individuals at risk for Alzheimer's disease: Neuroimaging-genetic evidence.
abstract: Clusterin (CLU) is recognized as a secreted protein that is related to the processes of inflammation and immunity in the pathogenesis of Alzheimer's disease (AD). The effects of the risk variant of the C allele at the rs11136000 locus of the CLU gene are associated with variations in the brain structure and function. However, the relationship of the CLU-C allele to architectural disruptions in resting-state networks in amnestic mild cognitive impairment (aMCI) subjects (i.e., individuals with elevated risk of AD) remains relatively unknown. Using resting-state functional magnetic resonance imaging and an imaging genetic approach, this study investigated whether individual brain functional networks, i.e., the default mode network (DMN) and the task-positive network, were modulated by the CLU-C allele (rs11136000) in 50 elderly participants, including 26 aMCI subjects and 24 healthy controls. CLU-by-aMCI interactions were associated with the information-bridging regions between resting-state networks rather than with the DMN itself, especially in cortical midline regions. Interestingly, the complex communications between resting-state networks were enhanced in aMCI subjects with the CLU rs11136000 CC genotype and were modulated by the degree of memory impairment, suggesting a reconstructed balance of the resting-state networks in these individuals with an elevated risk of AD. The neuroimaging-genetic evidence indicates that immunity factors may contribute to alterations in brain functional networks in aMCI. These findings add to the evidence that the CLU gene may represent a potential therapeutic target for slowing disease progression in AD.
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing 210009, China. Electronic address: baifeng515@126.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Bai
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Yonggui
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Chunming
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing 210009, China. Electronic address: janemengzhang@vip.163.com.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D000647:Amnesia / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D051152:Clusterin / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012306:Risk
chemical_list: C495242:CLU protein, human; D051152:Clusterin
keywords: Alzheimer’s disease; Amnestic mild cognitive impairment; Clusterin; Default mode network; Task-positive network