Abstract
Introduction: We evaluated the relationship between plasma levels of transactive response DNA binding protein of 43 kDa (TDP-43) and neuroimaging (magnetic resonance imaging [MRI]) measures of brain structure in aging. Methods: Plasma samples were collected from 72 non-demented older adults (age range 60–94 years) in the University of Kentucky Alzheimer's Disease Research Center cohort. Multivariate linear regression models were run with plasma TDP-43 level as the predictor variable and brain structure (volumetric or cortical thickness) measurements as the dependent variable. Covariates included age, sex, intracranial volume, and plasma markers of Alzheimer's disease neuropathological change (ADNC). Results: Negative associations were observed between plasma TDP-43 level and both the volume of the entorhinal cortex, and cortical thickness in the cingulate/parahippocampal gyrus, after controlling for ADNC plasma markers. Discussion: Plasma TDP-43 levels may be directly associated with structural MRI measures. Plasma TDP-43 assays may prove useful in clinical trial stratification. HIGHLIGHTS: Plasma transactive response DNA binding protein of 43 kDa (TDP-43) levels were associated with entorhinal cortex volume. Biomarkers of TDP-43 and Alzheimer's disease neuropathologic change (ADNC) may help distinguish limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) from ADNC. A comprehensive biomarker kit could aid enrollment in LATE-NC clinical trials.
Original language | English |
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Article number | e12437 |
Journal | Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring |
Volume | 15 |
Issue number | 2 |
DOIs | |
State | Published - Apr 1 2023 |
Bibliographical note
Publisher Copyright:© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.
Funding
The authors thank the dedicated research volunteers at our Sanders\u2010Brown Center on Aging. The authors also thank Beverly Meacham and Eric Foreman for assistance with MRI scanning, and Dr. David Powell for assistance with pulse sequence programming and selection. The authors declare no competing financial interests. This work was supported by the National Institutes of Health (grant numbers NIA P30 AG072946, NIA P30 AG028383 \u2010 15S1, NIA R01 AG055449, NIA R01 AG068055, NINDS RF1 NS122028, NIGMS S10 OD023573). The content is solely the responsibility of the authors and does not necessarily represent the official views of these granting agencies.
Funders | Funder number |
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National Institutes of Health (NIH) | |
National Institute on Aging | P30 AG028383 ‐ 15S1, R01 AG055449, R01 AG068055, P30 AG072946 |
National Institute on Aging | |
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council | RF1 NS122028 |
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council | |
National Institute of General Medical Sciences | S10 OD023573 |
National Institute of General Medical Sciences |
Keywords
- aging
- biomarker
- cortical thickness
- entorhinal cortex
- limbic-predominant age-related TDP-43 encephalopathy
- neuroimaging
- plasma transactive response DNA binding protein of 43 kDa
ASJC Scopus subject areas
- Clinical Neurology
- Psychiatry and Mental health