Association between APOE ε2 and Aβ burden in patients with Alzheimer- and vascular-type cognitive impairment

Abstract

Objective To investigate the association between APOE genotype and beta-amyloid (A beta) burden, as measured by PET in patients with subcortical vascular cognitive impairment (SVCI) and those with Alzheimer disease-related cognitive impairment (ADCI). Methods This was a cross-sectional study of 310 patients with SVCI and 999 with ADCI. To evaluate the effects of APOE genotype or diagnostic group on A beta positivity, we performed multivariate logistic regression analyses. Further distinctive underlying features of latent subgroups were examined by employing a latent class cluster analysis approach. Results In comparison with epsilon 3 homozygotes, in the ADCI group, epsilon 2 carriers showed a lower frequency of A beta positivity (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.23-0.79), while in the SVCI group, epsilon 2 carriers showed a higher frequency of A beta positivity (OR 2.26, 95% CI 1.02-5.01). In particular, we observed an interaction effect of epsilon 2 carrier status and diagnostic group on A beta positivity (OR 5.12, 95% CI 1.93-13.56), in that relative to epsilon 3 homozygotes, there were more A beta-positive epsilon 2 carriers in the SVCI group than in the ADCI group. We also identified latent subgroups of A beta-positive APOE epsilon 2 carriers with SVCI and A beta-positive APOE epsilon 4 carriers with ADCI. Conclusions Our findings suggest that APOE epsilon 2 is distinctly associated with A beta deposition in patients with SVCI and those with ADCI. Our findings further suggest that there is a distinctive subgroup of A beta-positive APOE epsilon 2 carriers with SVCI among patients with cognitive impairment.