title: Integration of Multilocus Genetic Risk into the Default Mode Network Longitudinal Trajectory during the Alzheimer's Disease Process.
abstract: The aim of the study was to investigate the cognitive significance of the changes in default mode network (DMN) during the process of Alzheimer's disease (AD) and the genetic basis that drives the alteration. Eighty-seven subjects with mild cognitive impairment (MCI) and 131 healthy controls (HC) were employed at baseline, and they had the genetic risk scores (GRS) based on the GWAS-validated AD-related top loci. Eleven MCIs who converted to AD (c-MCIs), 32 subjects who remained stable (nc-MCIs), and 56 HCs participated in the follow-up analyses after an average of 35 months. Decreased functional connectivity (FC) within temporal cortex was identified for MCIs at baseline, which was partially determined by the GRS; moreover, compensations may occur within the frontal-parietal brain to maintain relatively intact cognition. During the follow-ups, c-MCIs exhibited more FC declines within the prefrontal-parietal lobes and parahippocampal gyrus/hippocampus than the HCs and nc-MCIs. The GRS did not significantly vary among the three groups, whereas associations were identified at risky alleles and FC declines in all AD spectra. Interestingly, the influence of APOEɛ4 varied as the disease progressed; APOEɛ4 was associated with longitudinal FC decreases only for HCs in the single variance-based analyses and deteriorated DMN integration in nc-MCIs by combining the effects of other loci. However, the GRS without APOEɛ4 predicted FC decline for converters. It is suggested that the integration of multilocus genetic risk predicted the longitudinal trajectory of DMN and may be used as a clinical strategy to track AD progression.
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Su
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.|Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Shu
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Chunming
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Baoyu
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Bai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D003071:Cognition; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D012146:Rest
chemical_list: D053327:Apolipoprotein E4
keywords: Alzheimer’s disease; default mode network; functional MRI; genetic polymorphism; longitudinal investigation; mild cognitive impairment