Distinct neural correlates of episodic memory among apolipoprotein E alleles in cognitively normal elderly. Brain Imaging Behav 2019 Feb;13(1):255-269
Date
02/06/2018Pubmed ID
29396739Pubmed Central ID
PMC8061791DOI
10.1007/s11682-017-9818-4Scopus ID
2-s2.0-85045154865 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
The apolipoprotein E (APOE) ε4 and ε2 alleles are acknowledged genetic factors modulating Alzheimer's disease (AD) risk and episodic memory (EM) deterioration in an opposite manner. Mounting neuroimaging studies describe EM-related brain activity differences among APOE alleles but remain limited in elucidating the underlying mechanism. Here, we hypothesized that the APOE ε2, ε3, and ε4 alleles have distinct EM neural substrates, as a manifestation of degeneracy, underlying their modulations on EM-related brain activity and AD susceptibility. To test the hypothesis, we identified neural correlates of EM function by correlating intrinsic hippocampal functional connectivity networks with neuropsychological EM performances in a voxelwise manner, with 129 cognitively normal elderly subjects (36 ε2 carriers, 44 ε3 homozygotes, and 49 ε4 carriers). We demonstrated significantly different EM neural correlates among the three APOE allele groups. Specifically, in the ε3 homozygotes, positive EM neural correlates were characterized in the Papez circuit regions; in the ε4 carriers, positive EM neural correlates involved the lateral temporal cortex, premotor cortex/sensorimotor cortex/superior parietal lobule, and cuneus; and in the ε2 carriers, negative EM neural correlates appeared in the bilateral frontopolar, posteromedial, and sensorimotor cortex. Further, in the ε4 carriers, the interaction between age and EM function occurred in the temporoparietal junction and prefrontal cortex. Our findings suggest that the underlying mechanism of APOE polymorphism modulations on EM function and AD susceptibility is genetically related to the neural degeneracy of EM function across APOE alleles.
Author List
Shu H, Shi Y, Chen G, Wang Z, Liu D, Yue C, Ward BD, Li W, Xu Z, Chen G, Guo QH, Xu J, Li SJ, Zhang ZMESH terms used to index this publication - Major topics in bold
AgedAging
Alleles
Apolipoproteins E
Brain
Brain Mapping
Cohort Studies
Female
Heterozygote
Homozygote
Humans
Magnetic Resonance Imaging
Male
Memory, Episodic
Neural Pathways
Organ Size
Polymorphism, Genetic
