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Increased Alzheimer's disease neuropathology is associated with type 2 diabetes and ApoE ε.4 carrier status

Michael Malek-Ahmadi1, Thomas Beach, Aleksandra Obradov

  • 1The Cleo Robert Center for Clinical Research, Banner Sun Health Research Institute, Sun City, AZ 85351, USA.

Current Alzheimer Research
|May 1, 2013
PubMed
Abstract

Insights

Diabetes mellitus type 2 (DM2) does not alter Alzheimer's disease (AD) pathology overall. However, in AD patients with DM2, ApoE ε4 carriers show significantly greater neuropathology, suggesting DM2 exacerbates AD in the presence of ApoE ε4.

Area of Science:

  • Neuropathology
  • Neurodegenerative Diseases
  • Metabolic Disorders

Background:

  • Conflicting evidence exists regarding the association between Alzheimer's disease (AD) pathology and type 2 diabetes mellitus (DM2).
  • Some studies suggest comorbid DM2 reduces AD pathology, while others find no difference or increased neuropathology.
  • ApoE ε4 carriers with comorbid AD and DM2 may exhibit greater pathology than non-carriers.

Purpose of the Study:

  • To investigate the impact of DM2 on Alzheimer's disease (AD) neuropathology.
  • To determine if DM2 status influences plaque and tangle burden in AD cases.
  • To examine the combined effect of DM2 and ApoE ε4 carrier status on AD neuropathology.

Main Methods:

  • Analysis of clinically and pathologically confirmed AD cases with (n=40) and without (n=322) DM2 from the Banner Sun Health Research Institute Brain and Body Donation Program.
  • Comparison of plaque and tangle scores across brain regions, total plaque/tangle counts, and Braak scores between DM2+ and DM2- groups.
  • Logistic regression analyses to assess the independent and combined effects of DM2 and ApoE ε4 carrier status on neuropathological variables, controlling for age at death.

Main Results:

  • No significant differences in overall plaque and tangle pathology were observed between the DM2+ and DM2- groups.
  • Logistic regression revealed no association between DM2 status and total plaque or tangle counts, after accounting for ApoE ε4 carrier status and age at death.
  • Within the DM2+ group, ApoE ε4 carriers exhibited significantly greater plaque and tangle pathology compared to DM2+ non-carriers.

Conclusions:

  • The presence of DM2 does not significantly alter the overall burden of plaque and tangle pathology in Alzheimer's disease cases.
  • ApoE ε4 carrier status significantly exacerbates AD neuropathology in individuals with comorbid DM2.
  • These findings highlight a potential interaction between DM2, ApoE ε4, and AD neuropathological progression.

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