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Type: Journal article
Title: TDP-43 pathology in the population: prevalence and associations with dementia and age
Author: Keage, H.
Hunter, S.
Matthews, F.
Ince, P.
Hodges, J.
Hokkanen, S.
Highley, J.
Dening, T.
Brayne, C.
Citation: Journal of Alzheimer's Disease, 2014; 42(2):641-650
Publisher: IOS Press
Issue Date: 2014
ISSN: 1387-2877
Statement of
Hannah A.D. Keage, Sally Hunter, Fiona E. Matthews, Paul G. Ince, John Hodges, Suvi R.K. Hokkanen, J. Robin Highley, Tom Dening, Carol Brayne (and on behalf of the Cambridge City over 75s Cohort)
Abstract: Background: The significance of TDP-43 pathology in relation to aging and dementia in the population is unclear. Objective: We aimed to determine the prevalence of transactive response DNA-binding protein of 43 kDA (TDP-43) neuronal inclusions in a population-based sample, and associations with age group at death (≤90 and >90 years) and clinical dementia status prior to death. Further, we investigate associations between TDP-43 inclusions and other key dementia-related neuropathologies (plaques, tangles, and neuronal loss) within the hippocampus and entorhinal and temporal cortices. Methods: All brain donors within the Cambridge City over-75 s Cohort (CC75C), which is population-based and longitudinally tracked (n = 228), were included. Age at death ranged from 78 to 106 years. TDP-43 neuronal inclusions were assessed in the hippocampus, entorhinal cortex, and temporal cortex. These data were combined with existing clinical and neuropathological data. Results: TDP-43 neuronal inclusions were present in 27% of the sample, 36% of those with clinical dementia and 18% without dementia. Individuals who died later (>90 years) or with clinical dementia were more likely to show TDP-43 inclusions. Hippocampal and entorhinal TDP-43 inclusions were significantly associated with dementia severity and increasing age, taking into account other neuropathologies. TDP-43 neuronal inclusions appeared to be co-localize with severe neuronal loss. Conclusion: Findings indicate that hippocampal and entorhinal TDP-43 inclusions are important substrates of late onset dementia which appear to co-localize with severe neuronal loss, but not with Alzheimer's disease markers of amyloid and tau. This broadens the accepted view of TDP-43 pathology in dementias.
Keywords: Aging; Alzheimer’s disease; dementia; population; TDP-43
Rights: © 2014 – IOS Press and the authors. All rights reserved
DOI: 10.3233/JAD-132351
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