Direct ABCA7 high‐risk allele modulates medial temporal lobe dynamic network flexibility among cognitively healthy older African Americans

Abstract Background The medial temporal lobe (MTL) is the earliest region to display atrophy in Alzheimer’s disease (AD) 1 . Apolipoprotein E (APOE‐ε4) and ABCA7‐80 (rs115550680), two genes involved in lipid metabolism, are the strongest heritable contributors to AD in African Americans 2 . However, the longitudinal influence of these genes on MTL dynamic network flexibility, a novel neuroimaging marker of preclinical AD, is unknown. This study investigated the influence of APOE‐ε4 and ABCA7‐80 high‐risk alleles on MTL dynamic network flexibility longitudinally among cognitively healthy older African Americans. Method 135 participants (Age≥60, Mean baseline age = 68.07, SD baseline age = 7.31, Mean education = 13.56, SD education = 2.99) from the longitudinal study, Pathways to Healthy Aging in African Americans conducted at Rutgers University–Newark, completed saliva collection for genotyping and ≥1 neuroimaging visits across 4 years. Associations between APOE‐ ε4 and ABCA7‐80 on MTL dynamic network flexibility across time were assessed using linear mixed models. Result At baseline, the APOE‐ε4 allele had no significant relationship with MTL Dynamic Network Flexibility ( ß = 0.034, p = 0.297 ), whereas ABCA7‐80 was significantly associated with MTL Dynamic Network Flexibility ( ß = ‐0.124, p = 0.003 ). The ABCA7‐80 x time interaction was significantly associated with MTL Dynamic Network Flexibility ( ß = ‐0.074, p = 0.029 ), while there was no such significant ApoE‐ε4 x time interaction ( ß ApoE*Instance = ‐0.017, p ApoE*Instance = 0.53 ). Conclusion There were baseline and longitudinal differences on MTL dynamic network flexibility between ABCA7‐80 but not APOE‐ε4 risk groups among cognitively healthy older African Americans. ABCA7‐80 may have greater influence than APOE‐ε4 in the early MTL network changes associated with AD risk in older African Americans.