Convergent and divergent effects of apolipoprotein E ε4 and ε2 alleles on amygdala functional networks in non-demented older adults

Publication date: Available online 24 February 2017
Source:Neurobiology of Aging
Author(s): Liang Gong, Hao Shu, Cancan He, Qing Ye, Feng Bai, Chunming Xie, Zhijun Zhang
Traditionally, in the context of Alzheimer's disease (AD), the 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 AD 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 (aMCI) 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 aMCI patients. Our findings suggest that the APOEε2 and APOEε4 alleles produce both convergent and divergent topological effects on brain function.



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