Increased posterior default mode network activity and structural connectivity in young adult APOE-ε4 carriers: a multi-modal imaging investigation

Abstract Young adult APOE -e4 carriers show increased activity in posterior regions of the default mode network (pDMN), but how this is related to structural connectivity is unknown. Thirty young adults (one half of whom were APOE -e4 carriers; mean age 20 years) were scanned using both diffusion and functional magnetic resonance imaging. The parahippocampal cingulum bundle (PHCB) - which links pDMN and the medial temporal lobe (MTL) - was manually delineated in individual participants using deterministic tractography. Measures of tract microstructure (mean diffusivity, MD; fractional anisotropy, FA) were then extracted from these tract delineations. APOE -e4 carriers had lower MD and higher FA relative to non-carriers in PHCB, but not in a control tract (the inferior longitudinal fasciculus, ILF). Further, PHCB microstructure was selectively associated with pDMN (and MTL) activity during a scene discrimination task known to be sensitive to Alzheimer’s disease (AD). These findings are consistent with a lifespan view of AD risk, where early-life, connectivity-related changes in specific, vulnerable “hubs” (e.g., pDMN) lead to increased neural activity. Critically, such changes may reflect reduced network efficiency/flexibility in APOE -e4 carriers, which in itself may portend a faster decline in connectivity over the lifespan, and ultimately trigger early amyloid-s deposition in later-life.