ArticleFrontiers in aging neuroscience2026
Ventral hippocampal-postcentral gyrus functional connectivity mediates the association of APOE ε4 gene dose, depressive symptoms, and cognitive function in mild cognitive impairment with subsyndromal depression.
Article in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The apolipoprotein E (APOE) +4 allele is a major genetic risk factor for mild cognitive impairment (MCI) and is associated with hippocampal dysfunction. However, its effects on hippocampal subregional functional connectivity (FC) and clinical manifestations in MCI patients with subsyndromal depression (MCID) remain unclear. Methods: In this study, 88 patients with MCID were stratified into APOE+4 homozygotes ( Results: Compared with non-carriers, APOE +4 homozygotes showed decreased FC between the left vHIP and the left inferior temporal gyrus and right precentral gyrus, while heterozygotes showed decreased FC between the left vHIP and the right middle frontal gyrus and left cerebellum. In addition, APOE +4 homozygotes exhibited a gene dose-dependent reduction in FC between the vHIP and the left postcentral gyrus (PoCG) compared with heterozygotes. Importantly, vHIP-PoCG FC mediated the relationship between depressive symptoms and cognitive impairment, and between APOE +4 gene dose and cognitive impairment in MCID patients. Conclusion: These findings suggest that reduced vHIP-PoCG FC may represent a candidate neuroimaging correlate in MCID and may underlie APOE +4-related vulnerability to depressive and cognitive symptoms. Moreover, the mediating effect of vHIP-PoCG FC may partly account for the association among APOE +4 gene dose, depressive symptoms, and cognitive impairment in MCID.
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