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J Alzheimers Dis. 2014 Jun 13. [Epub ahead of print]

TDP-43 in the Population: Prevalence and Associations with Dementia and Age.

Author information

  • 1Cognitive Neuroscience Laboratory, School of Psychology, Social Work and Social Policy, University of South Australia, Australia.
  • 2Institute of Public Health, University of Cambridge, UK.
  • 3MRC Biostatistics Unit, Cambridge, UK.
  • 4Department of Neuroscience, Sheffield Institute of Translational Neuroscience, University of Sheffield, UK.
  • 5Neuroscience Australia, University of New South Wales, Australia.
  • 6Institute of Mental Health, Nottingham, UK.

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 co-localized 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; TDP-43; aging; dementia; population

PMID:
24927703
[PubMed - as supplied by publisher]
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