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 Citation (Scopus)

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

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Frontotemporal Dementia
Pathology
Frontotemporal Lobar Degeneration
Primary Progressive Aphasia
Mutation
DNA-Binding Proteins
Age of Onset
Autopsy
Phenotype

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

Cite this

Gefen, T., Ahmadian, S. S., Mao, Q., Kim, G., Seckin, M., Bonakdarpour, B., ... 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

Combined pathologies in FTLD-TDP types A and C. / Gefen, Tamar; Ahmadian, Saman S.; Mao, Qinwen; Kim, Garam; Seckin, Mustafa; Bonakdarpour, Borna; Ramos, Eliana Marisa; Coppola, Giovanni; Rademakers, Rosa V; Rogalski, Emily; Rademaker, Alfred; Weintraub, Sandra; Mesulam, M. Marsel; Geula, Changiz; Bigio, Eileen H.

In: Journal of Neuropathology and Experimental Neurology, Vol. 77, No. 5, 01.05.2018, p. 405-412.

Research output: Contribution to journalArticle

Gefen, T, Ahmadian, SS, Mao, Q, Kim, G, Seckin, M, Bonakdarpour, B, Ramos, EM, Coppola, G, Rademakers, RV, Rogalski, E, Rademaker, A, Weintraub, S, Mesulam, MM, Geula, C & Bigio, EH 2018, 'Combined pathologies in FTLD-TDP types A and C', Journal of Neuropathology and Experimental Neurology, vol. 77, no. 5, pp. 405-412. https://doi.org/10.1093/jnen/nly018
Gefen T, Ahmadian SS, Mao Q, Kim G, Seckin M, Bonakdarpour B et al. Combined pathologies in FTLD-TDP types A and C. Journal of Neuropathology and Experimental Neurology. 2018 May 1;77(5):405-412. https://doi.org/10.1093/jnen/nly018
Gefen, Tamar ; Ahmadian, Saman S. ; Mao, Qinwen ; Kim, Garam ; Seckin, Mustafa ; Bonakdarpour, Borna ; Ramos, Eliana Marisa ; Coppola, Giovanni ; Rademakers, Rosa V ; Rogalski, Emily ; Rademaker, Alfred ; Weintraub, Sandra ; Mesulam, M. Marsel ; Geula, Changiz ; Bigio, Eileen H. / Combined pathologies in FTLD-TDP types A and C. In: Journal of Neuropathology and Experimental Neurology. 2018 ; Vol. 77, No. 5. pp. 405-412.
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AU - Ahmadian, Saman S.

AU - Mao, Qinwen

AU - Kim, Garam

AU - Seckin, Mustafa

AU - Bonakdarpour, Borna

AU - Ramos, Eliana Marisa

AU - Coppola, Giovanni

AU - Rademakers, Rosa V

AU - Rogalski, Emily

AU - Rademaker, Alfred

AU - Weintraub, Sandra

AU - Mesulam, M. Marsel

AU - Geula, Changiz

AU - Bigio, Eileen H.

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N2 - 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.

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