Association between transactive response DNA-binding protein of 43 kDa type and cognitive resilience to Alzheimer's disease: a case-control study

Marina Buciuc, Jennifer L. Whitwell, Nirubol Tosakulwong, Stephen D. Weigand, Melissa E. Murray, Bradley F. Boeve, David S. Knopman, Joseph E. Parisi, Ronald C. Petersen, Dennis W. Dickson, Keith A. Josephs

Research output: Contribution to journalArticle

Abstract

Association between the transactive response DNA-binding protein of 43 kDa (TDP-43), its newly described types (type α/type β), and resilience to Alzheimer's disease neuropathological change (ADNC) defined as preservation of normal cognitive functioning despite advanced ADNC has been evaluated in this case-control study of 63 older adults. Twenty-one resilient to ADNC individuals were matched 1:2 to nonresilient (Alzheimer's dementia) using propensity scores, accounting for age at death, neuritic plaque density, and neurofibrillary tangle stage. Resilient and matched nonresilient participants were similar in terms of gender, apolipoprotein E ε4 carriership, education, occupation, AD, and other pathologies. Resilient participants had lower frequency of TDP-43 co-pathology compared to nonresilient (19% vs. 62%, p = 0.002). Among TDP-43-positive cases, TDP-43 type α inclusions were absent in resilient to ADNC participants and were dominant in matched nonresilient cases (65%, p = 0.03). TDP-43 and TDP-43 types appear to be one of the key pathological determinants of loss of cognitive resilience to ADNC and hence are important in the understanding of the clinical expression of ADNC.

Original languageEnglish (US)
Pages (from-to)92-97
Number of pages6
JournalNeurobiology of aging
Volume92
DOIs
StatePublished - Aug 2020

Keywords

  • Alzheimer's disease
  • Cognition
  • Normal aging
  • Resilience
  • TDP-43
  • TDP-43 types

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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