ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer's disease.

BACKGROUND:Since both APOE and ABCA7 protein expression may independently reduce neuritic plaque burden and reorganize fibrillar amyloid burden-mediated disruption of functional connectivity in the default mode network, we aimed to investigate the effect of the APOE-ABCA7 interaction on default mode network in Alzheimer's disease. METHODS:Two hundred and eighty-seven individuals with a diagnosis of typical Alzheimer's disease were included in this study. Memory was characterized and compared between APOE-ε4+ carriers and APOE-ε4 non-carriers within ABCA7 rs3764650T allele homozygous carriers and ABCA7 rs3764650G allele carriers, respectively. Two-way analysis of variance was used to identify a significant interaction effect between APOE (APOE-ε4+ carriers versus APOE-ε4 non-carriers) and ABCA7 (ABCA7 rs3764650T allele homozygous versus ABCA7 rs3764650G allele carriers) on memory scores and functional connectivity in each default mode network subsystem. RESULTS:In ABCA7 rs3764650G allele carriers, APOE-ε4+ carriers had lower memory scores (t (159) = - 4.879; P < 0.001) compared to APOE-ε4 non-carriers, but APOE-ε4+ carriers and APOE-ε4 non-carriers did not have differences in memory (P > 0.05) within ABCA7 rs3764650T allele homozygous carriers. There was a significant APOE-ABCA7 interaction effect on the memory (F3, 283 = 4.755, P = 0.030). In the default mode network anchored by the entorhinal seed, the peak neural activity of the cluster that was significantly associated with APOE-ABCA7 interaction effects (P = 0.00002) was correlated with the memory (ρ = 0.129, P = 0.030). CONCLUSIONS:Genetic-biological systems may impact disease presentation and therapy. Clarifying the effect of APOE-ABCA7 interactions on the default mode network and memory is critical to exploring the complex pathogenesis of Alzheimer's disease and refining a potential therapy.

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