Abstract
This study investigated the presence of combined pathologies in a large cohort of autopsies that show a primary pathologic diagnosis of phosphorylated 43-kDa TAR DNA-binding protein (FTLD-TDP), the majority of which portrayed clinical phenotypes consistent with primary progressive aphasia or behavioral variant frontotemporal dementia (bvFTD). Thirty-eight cases with FTLD-TDP (30 type-A and 8 type-C) were identified to determine characteristic differences between cases with and without combined pathologies. Findings indicated that combined pathologies co-occur with FTLD-TDP type-A at a high frequency (50%)-greater than when compared to FTLDTDP type-C cases (12.5%). Those with FTLD-TDP type-A and combined pathologies showed significantly longer lifespans (p < 0.05), and longer disease durations (p < 0.05), than those with only FTLDTDP type-A. Cases with FTLD-TDP type-A and known genetic mutations tended not to show combined pathology. Those with the GRN mutation and FTLD-TDP type-A showed a significantly younger age of onset (p < 0.05) and younger age at death (p < 0.01) compared to noncarriers. In 1 bvFTD case, we highlight the rare presence of "triple" FTLD-TDP type-A, FTLD-tau, and Alzheimer pathology. The ante- and post-mortem features associated with combined pathologies in FTLD-related disorders are of useful consideration in the stratification of patients to drug trials, and in the development of therapeutic targets for FTLD.
Original language | English (US) |
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Pages (from-to) | 405-412 |
Number of pages | 8 |
Journal | Journal of Neuropathology and Experimental Neurology |
Volume | 77 |
Issue number | 5 |
DOIs | |
State | Published - May 1 2018 |
Keywords
- Frontotemporal dementia
- Frontotemporal lobar degeneration
- Neuropathology
- Primary progressive aphasia
- TDP-43
ASJC Scopus subject areas
- General Medicine