Title:Increased Alzheimer’s Disease Neuropathology is Associated with Type 2 Diabetes and ApoE ε4 Carrier Status
Volume: 10
Issue: 6
Author(s): Michael Malek-Ahmadi, Thomas Beach, Aleksandra Obradov, Lucia Sue, Christine Belden, Kathryn Davis, Douglas G. Walker, LihFen Lue, Abdu Adem and Marwan N. Sabbagh
Affiliation:
Keywords:
Alzheimer’s disease, diabetes, neuropathology, ApoE, insulin resistance.
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.
