Association of Hemoglobin A1C With TDP-43 Pathology in Community-Based Elders. (1st June 2021)

• Record Type: Journal Article
• Authors: Oveisgharan, Shahram; Capuano, Ana W.; Nag, Sukriti; Agrawal, Sonal; Barnes, Lisa L.; Bennett, David A.; Arvanitakis, Zoe; Schneider, Julie A.
• Is Part Of: Neurology. Volume 96:Number 22(2021)
• Publication Date: 2021-06-01
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000012025
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To test the hypothesis that an inverse association exists between diabetes mellitus (DM) and hemoglobin A1C (A1C) with transactive response DNA binding protein 43 (TDP-43) levels in older adults. Methods: We leveraged antemortem and postmortem data of decedents from 3 community-based clinical–pathologic studies. DM status, A1C levels, and medications for DM were documented annually. TDP-43 cytoplasmic inclusions, evaluated in 6 brain regions using immunohistochemistry, were used to obtain a semiquantitative TDP-43 score (0–5) in each region, and scores were averaged across regions to obtain a TDP-43 severity score. We used linear regressions to test the association of DM and A1C with the TDP-43 severity score. Results: On average, participants (n = 817) were 90 years old at the time of death, three-fourths were women, and one-fourth had DM. The mean A1C was 6.0% (SD 0.6). TDP-43 was observed in 54% of participants, and the mean TDP-43 score was 0.7 (range 0–4.5). A higher level of A1C was associated with a lower TDP-43 score (estimate −0.156, SE 0.060, p = 0.009), while DM had a borderline inverse association with the TDP-43 score (estimate −0.163, SE 0.087, p = 0.060). The association of higher levels of A1C with lower TDP-43 scores persisted after further adjustment by APOE ε4, vascular risk factors, stroke, and hypoglycemic medications. Exclusion of the oldest old participants did not change the results. Conclusion: Overall, the results suggest that a high level of A1C is associated with less TDP-43 proteinopathy in older persons while the relationship of DM with TDP-43 needs further study.