Brian T. Gold

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.