Association between APOE ε2 and Aβ burden in patients with Alzheimer- and vascular-type cognitive impairment
Jin San Lee1, Hyejoo Lee1, Seongbeom Park2
1From the Department of Neurology (J.S.L., H.L., S.P., Y.C., Y.H.P., B.K.C., A.H., H.J.K., H.J., J.P.K., D.L.N., S.W.S.), Samsung Alzheimer Research Center (H.J.K., H.J., J.P.K., D.L.N., S.W.S.), and Statistics and Data Center (S.K., H.Y.), Samsung Medical Center; Department of Intelligent Precision Healthcare Convergence (S.W.S.), Sungkyunkwan University School of Medicine; Department of Health Sciences and Technology (S.W.S.), SAIHST, Sungkyunkwan University; Department of Neurology (J.S.L., K.-C.P.), Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul, Korea; Department of Neurology and Alzheimer Center (R.O.), Neuroscience Campus Amsterdam, VU University Medical Center, the Netherlands; Department of Neurology (S.H.C.), Chonnam National University Medical School, Gwangju; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon; Department of Neurology (Y.H.J.), Myungji Hospital, Goyang, Korea; Department of Neurology and Center for Neuroscience (C.D.), University of California, Davis; Department of Medicine (M.W.W.), University of California; and Department of Veterans Affairs Medical Center (M.W.W.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA. sangwonseo@empal.com hyejoo271@gmail.com.
Objective:
To investigate the association between APOE 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).
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% 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 APOE ε2 carriers with SVCI and Aβ-positive APOE ε4 carriers with ADCI.
Conclusions:
Our findings suggest that APOE 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 APOE ε2 carriers with SVCI among patients with cognitive impairment.
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