Temporal lobe functional activity and connectivity in young adult APOE ε4 carriers

Background: We sought to determine if the APOE 4 allele influences both the functional activation and connectivity of the medial temporal lobes (MTLs) during successful memory encoding in young adults. Methods: Twenty-four healthy young adults, i.e., 12 carriers and 12 noncarriers of the APOE 4 allele, were scanned in a subsequent-memory paradigm, using event-related functional magnetic resonance imaging. The neuroanatomic correlates of successful encoding were measured as greater neural activity for subsequently remembered versus forgotten task items, or in short, encoding success activity (ESA). Group differences in ESA within the MTLs, as well as whole-brain functional connectivity with the MTLs, were assessed. Results: In the absence of demographic or performance differences, APOE 4 allele carriers exhibited greater bilateral MTL activity relative to noncarriers while accomplishing the same encoding task. Moreover, whereas 4 carriers demonstrated a greater functional connectivity of ESA-related MTL activity with the posterior cingulate and other peri-limbic regions, reductions in overall connectivity were found across the anterior and posterior cortices. Conclusions: These results suggest that the APOE ε4 allele may influence not only functional activations within the MTL, but functional connectivity of the MTLs to other regions implicated in memory encoding. Enhanced functional connectivity of the MTLs with the posterior cingulate in young adult 4 carriers suggests that APOE may be expressed early in brain regions known to be involved in Alzheimer's disease, long before late-onset dementia is a practical risk or consideration. These functional connectivity differences may also reflect pleiotropic effects of APOE during early development.