Combined pathologies in FTLD-TDP types A and C

Tamar Gefen, Saman S. Ahmadian, Qinwen Mao, Garam Kim, Mustafa Seckin, Borna Bonakdarpour, Eliana Marisa Ramos, Giovanni Coppola, Rosa V Rademakers, Emily Rogalski, Alfred Rademaker, Sandra Weintraub, M. Marsel Mesulam, Changiz Geula, Eileen H. Bigio

Research output: Contribution to journalArticle

1 Scopus citations

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 languageEnglish (US)
Pages (from-to)405-412
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume77
Issue number5
DOIs
StatePublished - May 1 2018

Keywords

  • Frontotemporal dementia
  • Frontotemporal lobar degeneration
  • Neuropathology
  • Primary progressive aphasia
  • TDP-43

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Gefen, T., Ahmadian, S. S., Mao, Q., Kim, G., Seckin, M., Bonakdarpour, B., Ramos, E. M., Coppola, G., Rademakers, R. V., Rogalski, E., Rademaker, A., Weintraub, S., Mesulam, M. M., Geula, C., & Bigio, E. H. (2018). Combined pathologies in FTLD-TDP types A and C. Journal of Neuropathology and Experimental Neurology, 77(5), 405-412. https://doi.org/10.1093/jnen/nly018