Distinct patterns of brain activity in young carriers of the APOE-ε4 allele

The APOE epsilon 4 allele is a risk factor for late-life pathological changes that is also associated with anatomical and functional brain changes in middle-aged and elderly healthy subjects. We investigated structural and functional effects of the APOE polymorphism in 18 young healthy APOE epsilon 4-carriers and 18 matched noncarriers (age range: 20-35 years). Brain activity was studied both at rest and during an encoding memory paradigm using blood oxygen level-dependent fMRI. Resting fMRI revealed increased default mode network'' (involving retrosplenial, medial temporal, and medial-prefrontal cortical areas) coactivation in epsilon 4-carriers relative to noncarriers. The encoding task produced greater hippocampal activation in epsilon 4-carriers relative to noncarriers. Neither result could be explained by differences in memory performance, brain morphology, or resting cerebral blood flow. The APOE epsilon 4 allele modulates brain function decades before any clinical or neurophysiological expression of neurodegenerative processes.