Convergent and divergent effects of apolipoprotein E ε4 and ε2 alleles on amygdala functional networks in nondemented older adults.
Traditionally, in the context of Alzheimer's disease, the apolipoprotein E ε2 (APOEε2) allele is a protective factor and the APOEε4 allele is a destructive factor. However, this inverse relationship has recently been challenged, and the neural mechanisms underlying the effects of APOE genotype on Alzheimer's disease remain unclear. A resting-state functional magnetic resonance imaging study was conducted to investigate the effects of APOE genotype and age on amygdala functional connectivity (AFC) networks in 84 patients with amnestic mild cognitive impairment and 124 cognitively normal order adults. The results indicated that the APOEε2 and APOEε4 alleles produced convergent effects in the right AFC network but divergent effects in the left AFC network. As age increased, APOEε2 carriers showed stable AFC, whereas APOEε4 carriers exhibited decreased AFC in all participants. Furthermore, mediation analysis revealed that connectivity strength regulates the effects of APOE genotype and age on cognitive function in amnestic mild cognitive impairment patients. Our findings suggest that the APOEε2 and APOEε4 alleles produce both convergent and divergent topological effects on brain function.
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Liang
L
Gong
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China; Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA.
Hao
H
Shu
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Cancan
C
He
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Qing
Q
Ye
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China; Neuropsychiatric Institute, Affiliated ZhongDa Hospital, Southeast University, Nanjing, Jiangsu, China.
Feng
F
Bai
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China; Neuropsychiatric Institute, Affiliated ZhongDa Hospital, Southeast University, Nanjing, Jiangsu, China. Electronic address: chmxie@163.com.
Chunming
C
Xie
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China; Neuropsychiatric Institute, Affiliated ZhongDa Hospital, Southeast University, Nanjing, Jiangsu, China. Electronic address: janemengzhang@vip163.com.
Zhijun
Z
Zhang
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000502:physiology*; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics; D000679:Amygdala / Q000502:physiology* / Q000503:physiopathology*; D053329:Apolipoprotein E2 / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000235:genetics* / Q000523:psychology*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged
D053329:Apolipoprotein E2; D053327:Apolipoprotein E4
Aging; Alzheimer's disease; Amygdala; Apolipoprotein E; Functional connectivity