Key result
Young adult APOE-ε4 carriers demonstrated lower mean diffusivity and higher fractional anisotropy in the parahippocampal cingulum bundle relative to noncarriers.
Cross-Sectional (n=30)
Young adult APOE-ε4 carriers exhibit early structural connectivity changes in the parahippocampal cingulum bundle that correlate with increased default mode network activity, suggesting early-life network alterations related to Alzheimer's disease risk.
PHCB microstructure alterations may underlie pDMN hyperactivity in young APOE-ε4 carriers; leaves open early AD vulnerability mechanisms.
Young adult APOE-ε4 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-ε4 carriers; mean age 20 years) were scanned using both diffusion and functional magnetic resonance imaging. The parahippocampal cingulum bundle (PHCB)-which links the pDMN and the medial temporal lobe-was manually delineated in individual participants using deterministic tractography. Measures of tract microstructure (mean diffusivity and fractional anisotropy) were then extracted from these tract delineations. APOE-ε4 carriers had lower mean diffusivity and higher fractional anisotropy relative to noncarriers in PHCB, but not in a control tract (the inferior longitudinal fasciculus). Furthermore, PHCB microstructure was selectively associated with pDMN (and medial temporal lobe) activity during a scene discrimination task known to be sensitive to Alzheimer's disease. These findings are consistent with a lifespan view of Alzheimer's disease 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-ε4 carriers, which in itself may portend a faster decline in connectivity over the lifespan and ultimately trigger early amyloid-β deposition in later life.
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Hodgetts et al. (2018) conducted a cross-sectional in Healthy young adults (n=30). APOE-ε4 carrier status vs. Noncarriers was evaluated on Tract microstructure (mean diffusivity and fractional anisotropy) in the parahippocampal cingulum bundle. Young adult APOE-ε4 carriers demonstrated lower mean diffusivity and higher fractional anisotropy in the parahippocampal cingulum bundle relative to noncarriers.