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 language | English (US) |
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Pages (from-to) | 92-97 |
Number of pages | 6 |
Journal | Neurobiology of aging |
Volume | 92 |
DOIs | |
State | Published - Aug 2020 |
Keywords
- Alzheimer's disease
- Cognition
- Normal aging
- Resilience
- TDP-43
- TDP-43 types
ASJC Scopus subject areas
- General Neuroscience
- Aging
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology