O4‐03‐05: APOE‐ε4 genotype affects brain function without apparent micro‐ and macrostructural changes in young adults: A multimodal fMRI, DTI and VBM study

Abstract

The Apolipoprotein E4 (APOE-ε4) genotype is the highest single genetic risk factor for sporadic Alzheimer's Disease (AD) and has been associated with higher rates of brain atrophy, amyloid deposition, and decreased fiber tract integrity in older subjects. While some functional neuroimaging studies in young APOE-ε4 carriers suggest altered neuronal activation patterns during episodic memory tasks, it is not clear whether these functional changes precede micro- and macrostructural changes associated with the APOE-ε4 genotype. The aim of the present study was to assess the differential influence of the ApoE4 genotype on 1.) functional neuronal activation patterns associated with episodic memory, 2.) microstructural integrity of brain white matter and 3.) macrostructural volume of grey matter in young healthy adults. 22 APOE-ε4 carriers (26.8. ± 5.3 y) and 22 non-carriers (APOE-ε3/3), matched in age and education underwent functional MRI (fMRI), high-resolution 3D-anatomical MRI imaging, diffusion tensor imaging (DTI), and extensive neuropsychological assessment. Functional activation during the encoding stage of an established face-name association task was analyzed using BrainVoyager QX 2.2. Voxel-Based Morphometry (VBM) was used to identify areas of APOE-ε4-related differences in brain grey matter volume. Additionally, DTI data were analysed with Tract-Based Spatial Statistics (TBSS) to reveal possible differences in fractional anisotropy (FA) between groups. The neuropsychological assessment did not show an influence of ApoE4 on measures of memory or attention. Structural analyses with VBM and DTI did not reveal any significant differences in gray matter and white matter volume or in FA between groups. In contrast to the neuropsychological and structural findings, there was an effect of APOE-ε4 on functional activation patterns during episodic memory associative encoding. Compared to the homozygote APOE-ε3 group, APOE-ε4 carriers showed reduced task-induced activation in dorsolateral prefrontal cortex bilaterally and in the left parietal cortex. These results suggest that the APOE-ε4 genotype affects neuronal function in young adults but not micro- and macrostructure, as detectable with VBM and TBSS. These findings are relevant to the question of potential preclinical disease-driving factors, providing a rationale for further studies assessing functional neuronal aberration as a possible independent risk factor for the development of subsequent neurodegeneration at older age.