Past studies of Alzheimer’s disease (AD) pathology association with diabetes mellitus type 2 (DM2) have provided conflicting results. While several studies indicate that subjects with comorbid AD and DM2 have less AD pathology, others have found no significant differences in AD pathology between the two groups. Other studies have indicated that individuals with AD and DM2 have significantly greater neuropathology than AD individuals who do not have DM2. Additional research has demonstrated that ApoE ε4 carriers with AD and DM2 have significantly greater pathology than ApoE ε4 non-carriers.
Data on clinically and pathologically diagnosed Alzheimer’s disease (NINDS-ADRDA clinically and NIA Reagan intermediate or high pathologically) with DM2 (n= 40) and those without DM2 (n= 322) from the Banner Sun Health Research Institute Brain and Body Donation Program were obtained for this study. Plaque and tangle scores from the frontal, parietal, temporal, entorhinal and hippocampal regions were compared between the DM2+ and DM2 − groups. In addition, total plaque count, total tangle count, and Braak scores were also compared between groups. Similar analyses were carried out to discern differences between ApoE ε4 carriers and non-carriers with AD and DM2.
There were no significant differences in plaque and tangle pathology between DM2+ and DM2 − groups. Logistic regression analyses, which accounted for the effects of ApoE ε4 carrier status and age at death, found no association between total plaque [OR 1.05 (0.87, 1.27), p = .60] or total tangle [OR 0.97 (0.89, 1.07) p = .58] counts and DM2 status. Chi-square analysis found no significant association between ApoE ε4 carrier status and DM2 status [χ2 = 0.30 (df = 1), p = .58]. Within the DM2+ group, ApoE ε4 carriers had significantly greater plaque and tangle pathology when compared to DM2+ ApoE ε4 non-carriers.
Overall, the presence of DM2 does not affect plaque and tangle burden in a sample of clinically and pathologically confirmed AD cases. Among AD individuals with DM2, those who are ApoE ε4 carriers had significantly greater neuropathology than ApoE ε4 non-carriers. The presence of ApoE ε4 appears to exacerbate AD neuropathology in the presence of DM2.