TitleCombined Pathologies in FTLD-TDP Types A and C.
Publication TypeJournal Article
Year of Publication2018
AuthorsGefen 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
JournalJ Neuropathol Exp Neurol
Volume77
Issue5
Pagination405-412
Date Published2018 May 01
ISSN1554-6578
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.

DOI10.1093/jnen/nly018
Alternate JournalJ. Neuropathol. Exp. Neurol.
PubMed ID29584904
Grant ListK23 DC014303 / DC / NIDCD NIH HHS / United States
P30 AG013854 / AG / NIA NIH HHS / United States
R01 NS085770 / NS / NINDS NIH HHS / United States