IC-P3-193: Impact of apolipoprotein E gene polymorphism on cerebral white matter integrity in Alzheimer's disease: DTI study

Abstract

Apolipoprotein E (APOE) ϵ4 allele is a very well-known genetic risk factor of Alzheimer's disease (AD). Recent histopatholgical and MRI studies in patients with AD demonstrated alterations of white matter, as well as gray matter. This study aimed to investigate possible associations between cerebral white matter changes and APOE genotype in early stage AD. The authors used Diffusion Tensor Imaging (DTI) to explore cerebral white matter changes to detect pathological processes. 26 AD participants were included in the study of which 13 were APOE ϵ4 carriers and age-, gender-, and severity-matched 13 were APOE ϵ4 non-carriers. All AD individuals were met for NINCDS-ADRDA Diagnostic Criteria of probable AD and their global scores of Clinical Dementia Rating scale were 0.5 or 1. Voxel-based comparisons for the Fractional Anisotropy (FA) and Mean Diffusivity (MD) were performed between APOE ϵ4 carriers and ϵ4 non-carriers using SPM5. FA value was significantly lower in APOE ϵ4 carriers than APOE ϵ4 non-carriers in the bilateral temporal white matter, right cingulate white matter, left parahippocampal white matter, right postcentral parietal white matter, bilateral frontal and occipital white matter. Compared to APOE ϵ4 non-carriers, APOE ϵ4 carriers had significant increase of the MD value in the bilateral medial frontal white matter, right inferior frontal white matter, left precentral white matter, and left posterior cingulate white matter (p<0.005, uncorrected for multiple comparisons). Although the exact mechanism underlying vulnerability of white matter tracts in APOE ϵ4 carriers is still unclear, these findings indicate that increased genetic risk by APOE ϵ4 allele is associated with advanced regional alterations of white matter, as well as gray matter changes, in early stage AD.