Differential effects of the ApoE4 genotype on brain structure and function

•We used a multimodal approach to investigate brain structure and function.•There were memory related alterations in neuronal activations in ApoE4 carriers.•No alterations in brain micro- and macrostructure were found in ApoE4 carriers.•Cognitive performance was equal in ApoE4 carriers and noncarriers.

The apolipoprotein E ε4 allele is a well established genetic risk factor for sporadic Alzheimer's disease. It is associated with structural and functional brain changes in healthy young, middle-aged and elderly subjects. In the current study, we assessed the impact of the ApoE genotype on brain macro- and microstructure, cognitive functioning and brain activity in fifty healthy young subjects (25 ApoE ε4 (ε4 +) carriers and 25 non-carriers (ε4 −), mean age 26.4 ± 4.6 years). We used diffusion tensor imaging (DTI) and voxel based morphometry (VBM) to assess brain structure, an extensive neuropsychological battery to test cognitive functioning and event-related functional magnetic resonance imaging (fMRI) to capture brain activity during episodic memory encoding and retrieval. ApoE ε4 carriers differed from non-carriers in fMRI activations but not in cognitive performance nor in brain micro- and macrostructure. These results suggest functional alterations in the episodic memory network that are modulated by the ε4 allele and might precede clinical or structural neurodegeneration.