Abstract
BackgroundSince 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.MethodsTwo 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.ResultsIn 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).ConclusionsGenetic-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.
Highlights
Since both Apolipoprotein E (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
Pathogenic studies show that the APOE-ε4 allele is associated with reduction of APOE protein [3] that subsequently leads to several Alzheimer’s disease (AD)-relevant changes, including memory impairment, synaptogenesis dysfunction, tau hyperphosphorylation [4], and amyloid β (Aβ) plaque deposition [5], which together may hasten the progression of AD
In the default mode network (DMN) anchored by the right entorhinal seed, the peak neural activity of the cluster that was significantly associated with APOE-ABCA7 interaction effects were correlated with memory scores in the Chinese Version Verbal Learning Test (CVVLT)-10 min and CVVLT-cued tests (P < 0.05; Fig. 1)
Summary
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. Presence of an APOE-ε4 allele increases the risk of AD and facilitates the rate of cognitive decline during the course of disease [2]. Because inducible expression of APOE to facilitate Aβ clearance [6], reorganize synaptic disruption [7], and slow cognitive decline [8] may provide novel approaches to AD treatment, there is a critical need to dissect the effects of APOE on AD biomarkers. In rs-fMRI studies, changes in DMN connectivity due to the APOE-ε4 allele have not been determined, as one study showed no APOE-related differences in functional connectivity [10], a second study reported significantly lower DMN connectivity in APOE-ε4 allele carriers than in APOE-ε3 homozygotes [11], and a third study demonstrated increased DMN connectivity in APOE-ε4 allele carriers [12]
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