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

Description

Yang Du and colleagues traced a brain connection carrying the combined weight of a risk gene, low mood, and fading memory. The APOE ε4 gene variant is the strongest common genetic risk for Alzheimer's disease. Their 2026 study scanned eighty-eight patients with mild cognitive impairment together with mild, below-threshold depression. Patients split by gene dose: twelve carried two copies, thirty-one one, and forty-five none.

Carriers showed weaker resting links between the lower hippocampus and other regions, with the pattern deepening as dose rose. One link stood out, running to the postcentral gyrus, a strip handling body sensation. That link carried the statistical bridge both ways: between gene dose and thinking scores, and between depressive symptoms and thinking scores. The authors propose it as a candidate imaging marker for this blended syndrome. A marker that sits on both paths, they argue, could guide who gets watched or treated first.

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Source: https://europepmc.org/article/MED/PMC13438303