Association of Hemoglobin A1C With TDP-43 Pathology in Community-Based Elders.

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.

• Authors: Shahram Oveisgharan, Ana W Capuano, Sukriti Nag, Sonal Agrawal, Lisa L Barnes, David A Bennett, Zoe Arvanitakis, Julie A Schneider
• Journal: Neurology (Neurology) Vol. 96 Issue 22 Pg. e2694-e2703 (May 31 2021) ISSN: 1526-632X [Electronic] United States
• PMID: 33853892 (Publication Type: Journal Article)
• Copyright: © 2021 American Academy of Neurology.