Distinct patterns of brain activity in young carriers of theAPOE-ε4 allele

<jats:p>The<jats:italic>APOE</jats:italic>ε4 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<jats:italic>APOE</jats:italic>polymorphism in 18 young healthy<jats:italic>APOE</jats:italic>ε4-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 ε4-carriers relative to noncarriers. The encoding task produced greater hippocampal activation in ε4-carriers relative to noncarriers. Neither result could be explained by differences in memory performance, brain morphology, or resting cerebral blood flow. The<jats:italic>APOE</jats:italic>ε4 allele modulates brain function decades before any clinical or neurophysiological expression of neurodegenerative processes.</jats:p>