Title | Combined Pathologies in FTLD-TDP Types A and C. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Gefen T, Ahmadian SS, Mao Q, Kim G, Seckin M, Bonakdarpour B, Ramos EMarisa, Coppola G, Rademakers R, Rogalski E, Rademaker A, Weintraub S, Mesulam M-M, Geula C, Bigio EH |
Journal | J Neuropathol Exp Neurol |
Volume | 77 |
Issue | 5 |
Pagination | 405-412 |
Date Published | 2018 May 01 |
ISSN | 1554-6578 |
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 FTLD-TDP 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 FTLD-TDP 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. |
DOI | 10.1093/jnen/nly018 |
Alternate Journal | J. Neuropathol. Exp. Neurol. |
PubMed ID | 29584904 |
Grant List | K23 DC014303 / DC / NIDCD NIH HHS / United States P30 AG013854 / AG / NIA NIH HHS / United States R01 NS085770 / NS / NINDS NIH HHS / United States |