Objective: To investigate the association between apolipoprotein E (APOE) genotype and amyloid-β (Aβ) burden, as measured by PET in patients with subcortical vascular cognitive impairment (SVCI) and those with Alzheimer’s 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 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.

Results: In comparison with ε3 homozygotes, in the ADCI group, ε2 carriers showed a lower frequency of Aβ-positivity (odds ratio [OR] 0.43, 95% 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 APOE ε2 carriers with SVCI and Aβ-positive APOE ε4 carriers with ADCI.

Conclusions: Our findings suggest that APOE ε2 shows 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 APOE ε2 carriers with SVCI among patients with cognitive impairments.