title: The apolipoprotein E gene affects the three-year trajectories of compensatory neural processes in the left-lateralized hippocampal network.
abstract: Previous cross-sectional studies that investigated the effects of apolipoprotein E (ApoE) ε4 status on hippocampal networks have shown inconsistent results. Aging is a well-known risk factor for Alzheimer's disease (AD) and could strongly interact with ApoE-related vulnerabilities to affect AD risk. However, no longitudinal data have been published regarding the interaction of the ApoE genotype and aging on hippocampal networks. Fifty-one patients with amnestic-type mild cognitive impairment (aMCI) and 64 matched cognitively normal elderly subjects underwent resting-state fMRI scans and neuropsychological tests at baseline and at a 35-month follow-up. Hippocampal resting-state functional connectivity (FC) data were analyzed utilizing a mixed analysis of covariance with ApoE genotype, time points and disease as fixed factors, controlling for age, sex and years of education. The notable finding was that the FC between the left hippocampus and right frontal regions for ε4 carriers longitudinally increased in the normal subjects, but decreased in aMCI patients, whereas the FC for non-carriers was maintained in normal subjects but increased in aMCI patients. Specifically, the longitudinal increases in hippocampal FC with the right inferior frontal gyrus were positively correlated with the changes in episodic memory test scores in non-carriers with aMCI. The interaction between the ApoE genotype, aging and disease suggested that aging should be considered a key regulator of the impact of the ApoE genotype on the phenotypic variants of AD. These findings also demonstrated that compensatory neural processes were accelerated in genetically high risk individuals, but could be subsequently exhausted with the onset of cognitive impairment.
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Su
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Shu
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Gong
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.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, 210009, China. baifeng515@126.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Bai
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics* / Q000502:physiology*; D001057:Apolipoproteins E / Q000235:genetics*; D001931:Brain Mapping; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D004522:Educational Status; D005260:Female; D005500:Follow-Up Studies; D007839:Functional Laterality; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006579:Heterozygote; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D009483:Neuropsychological Tests; D012146:Rest; D012727:Sex Characteristics
chemical_list: D001057:Apolipoproteins E
keywords: Apolipoprotein E; Compensation; Hippocampus; Longitudinal study; Resting-state functional connectivity