Increased Alzheimer’s Disease Neuropathology is Associated with Type 2 Diabetes and ApoE ε4 Carrier Status

Michael      Malek-Ahmadi; Thomas      Beach; Aleksandra      Obradov; Lucia      Sue; Christine      Belden; Kathryn      Davis; Douglas   G.   Walker; LihFen      Lue; Abdu      Adem; Marwan   N.   Sabbagh

Abstract

Background: Past studies investigating the association between Alzheimer’s disease (AD) pathology and 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.

Methods: Data on clinically and pathologically diagnosed Alzheimer’s disease cases (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 conducted to determine the effect of ApoE ε4 carrier status on the neuropathological variables while also accounting for and DM2 status.

Results: The DM2+ and DM2 – groups showed no significant differences on plaque and tangle pathology. 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 = 0.60] or total tangle [OR 0.97 (0.89, 1.07) p = 0.58] counts and DM2 status. ApoE ε4 carrier status was not significantly associated with DM2 status [Χ2 = 0.30 (df = 1), p = 0.58]. Within the DM2+ group, significantly greater plaque and tangle pathology was found for ApoE ε4 carriers in relation to DM2+ ApoE ε4 non-carriers.

Conclusion: 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 those who do not carry an ApoE ε4 allele. Positive DM2 status appears to exacerbate AD neuropathology in the presence of ApoE ε4.

Keywords: Alzheimer’s disease, diabetes, neuropathology, ApoE, insulin resistance.

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