TDP-43 frontotemporal lobar degeneration and autoimmune disease

Zachary A. Miller, Katherine P. Rankin, Neill R. Graff-Radford, Leonel T. Takada, Virginia E. Sturm, Clare M. Cleveland, Lindsey A. Criswell, Philipp A. Jaeger, Trisha Stan, Kristin A. Heggeli, Sandy Chan Hsu, Anna Karydas, Baber K. Khan, Lea T. Grinberg, Maria Luisa Gorno-Tempini, Adam L. Boxer, Howard J. Rosen, Joel H. Kramer, Giovanni Coppola, Daniel H. GeschwindRosa Rademakers, William W. Seeley, Tony Wyss-Coray, Bruce L. Miller

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


Background: The aetiology and pathogenesis of non-genetic forms of frontotemporal dementia (FTD) is unknown and even with the genetic forms of FTD, pathogenesis remains elusive. Given the association between systemic inflammation and other neurodegenerative processes, links between autoimmunity and FTD need to be explored. Objective: To describe the prevalence of systemic autoimmune disease in semantic variant primary progressive aphasia (svPPA), a clinical cohort, and in progranulin (PGRN) mutation carriers compared with neurologically healthy normal controls (NC) and Alzheimer's disease (AD) as dementia controls. Design Case control. Setting Academic medical centres. Participants 129 svPPA, 39 PGRN, 186 NC and 158 AD patients underwent chart review for autoimmune conditions. A large subset of svPPA, PGRN and NC cohorts underwent serum analysis for tumour necrosis factor α(TNF-α) levels. Outcome measures χ2 Comparison of autoimmune prevalence and follow-up logistic regression. Results: There was a significantly increased risk of autoimmune disorders clustered around inflammatory arthritides, cutaneous disorders and gastrointestinal conditions in the svPPA and PGRN cohorts. Elevated TNF-α levels were observed in svPPA and PGRN compared with NC. Conclusions: svPPA and PGRN are associated with increased prevalence of specific and related autoimmune diseases compared with NC and AD. These findings suggest a unique pattern of systemic inflammation in svPPA and PGRN and open new research avenues for understanding and treating disorders associated with underlying transactive response DNA-binding protein 43 aggregation.

Original languageEnglish (US)
Pages (from-to)956-962
Number of pages7
JournalJournal of Neurology, Neurosurgery and Psychiatry
Issue number9
StatePublished - Sep 2013

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health


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