Association between <i>APOE</i> ε2 and Aβ burden in patients with Alzheimer- and vascular-type cognitive impairment.

Abstract

To investigate the association between <i>APOE</i> genotype and β-amyloid (Aβ) burden, as measured by PET in patients with subcortical vascular cognitive impairment (SVCI) and those with Alzheimer disease-related cognitive impairment (ADCI). This was a cross-sectional study of 310 patients with SVCI and 999 with ADCI. To evaluate the effects of <i>APOE</i> genotype or diagnostic group on Aβ positivity, we performed multivariate logistic regression analyses. Further distinctive underlying features of latent subgroups were examined by employing a latent class cluster analysis approach. In comparison with ε3 homozygotes, in the ADCI group, ε2 carriers showed a lower frequency of Aβ positivity (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.23-0.79), while in the SVCI group, ε2 carriers showed a higher frequency of Aβ positivity (OR 2.26, 95% CI 1.02-5.01). In particular, we observed an interaction effect of ε2 carrier status and diagnostic group on Aβ positivity (OR 5.12, 95% CI 1.93-13.56), in that relative to ε3 homozygotes, there were more Aβ-positive ε2 carriers in the SVCI group than in the ADCI group. We also identified latent subgroups of Aβ-positive <i>APOE</i> ε2 carriers with SVCI and Aβ-positive <i>APOE</i> ε4 carriers with ADCI. Our findings suggest that <i>APOE</i> ε2 is distinctly associated with Aβ deposition in patients with SVCI and those with ADCI. Our findings further suggest that there is a distinctive subgroup of Aβ-positive <i>APOE</i> ε2 carriers with SVCI among patients with cognitive impairment.