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Differential impact of sub‐threshold amyloid‐beta deposition on regional homogeneity for cognitively normal older adults according to APOE genotype: Whole brain voxel‐wise analysis
Author(s) -
Kang Dong Woo,
Lim Hyun Kook,
Wang ShengMin,
Um Yoo Hyun
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.057718
Subject(s) - apolipoprotein e , positron emission tomography , pittsburgh compound b , temporal lobe , psychology , alzheimer's disease , voxel , medicine , neuroscience , disease , radiology , epilepsy
Background Previous research has demonstrated that sub‐threshold amyloid‐beta retention is related to cognitive performance, functional brain change, and further amyloid‐beta /tau accumulation. However, little research has investigated an effect of APOE genotype on the association between sub‐threshold amyloid‐beta deposition and intra‐regional brain activity in the earliest stage of Alzheimer’s disease (AD). This study set out to evaluate the impact of sub‐threshold global and regional amyloid‐beta retention on intra‐regional brain activity, measured by regional homogeneity (ReHo), in cognitively normal older adults, according to APOE ε4‐allele status. Method Cognitively normal older adults with and without APOE ε4 allele (carrier, n=32; non‐carrier, n=80) underwent functional magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans with [ 18 F] flutemetamol. Whole‐brain voxel wise analysis was conducted for evaluating the sub‐threshold Ab deposition‐by‐ APOE genotype interaction for ReHo, adjusting for age, sex, and education years. Result Sub‐threshold amyloid‐beta deposition in temporal lobe showed a significant interaction with APOE genotype for ReHo of left calcarine fissure and surrounding cortex, cerebellum 7, and cerebellum 6 (FDR‐adjusted p < 0.05, cluster size > 100 voxels). Cognitively normal older adults with APOE ε4 allele exhibited a positive relationship between sub‐threshold amyloid‐beta retention in temporal lobe and ReHo, while those without APOE ε4 allele showing an opposing association. Conclusion Thus, even sub‐threshold amyloid‐beta deposition has a differential impact on ReHo according to the representative AD risk factor, APOE ε4 allele in the earliest phase of AD. These results could contribute to the deeper understanding of the initial pathogenesis of AD.