TREM2 in neurodegeneration: Evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson's disease

Sruti Rayaprolu, Bianca Mullen, Matt Baker, Timothy Lynch, Elizabeth Finger, William W. Seeley, Kimmo J. Hatanpaa, Catherine Lomen-Hoerth, Andrew Kertesz, Eileen H. Bigio, Carol Lippa, Keith A. Josephs, David S. Knopman, Charles L. White, Richard Caselli, Ian R. Mackenzie, Bruce L. Miller, Magdalena Boczarska-Jedynak, Grzegorz Opala, Anna Krygowska-WajsMaria Barcikowska, Steven G. Younkin, Ronald C. Petersen, Nilüfer Ertekin-Taner, Ryan J. Uitti, James F. Meschia, Kevin B. Boylan, Bradley F. Boeve, Neill R. Graff-Radford, Zbigniew K. Wszolek, Dennis W. Dickson, Rosa Rademakers, Owen A. Ross

Research output: Contribution to journalArticlepeer-review

229 Scopus citations


Background: A rare variant in the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) gene has been reported to be a genetic risk factor for Alzheimer's disease by two independent groups (Odds ratio between 2.9-4.5). Given the key role of TREM2 in the effective phagocytosis of apoptotic neuronal cells by microglia, we hypothesized that dysfunction of TREM2 may play a more generalized role in neurodegeneration. With this in mind we set out to assess the genetic association of the Alzheimer's disease-related risk variant in TREM2 (rs75932628, p.R47H) with other related neurodegenerative disorders. Results: The study included 609 patients with frontotemporal dementia, 765 with amyotrophic lateral sclerosis, 1493 with Parkinson's disease, 772 with progressive supranuclear palsy, 448 with ischemic stroke and 1957 controls subjects free of neurodegenerative disease. A significant association was observed for the TREM2 p.R47H substitution in susceptibility to frontotemporal dementia (OR = 5.06; p-value = 0.001) and Parkinson's disease (OR = 2.67; p-value = 0.026), while no evidence of association with risk of amyotrophic lateral sclerosis, progressive supranuclear palsy or ischemic stroke was observed. Conclusions: Our results suggest that the TREM2 p.R47H substitution is a risk factor for frontotemporal dementia and Parkinson's disease in addition to Alzheimer's disease. These findings suggest a more general role for TREM2 dysfunction in neurodegeneration, which could be related to its role in the immune response.

Original languageEnglish (US)
Article number19
JournalMolecular neurodegeneration
Issue number1
StatePublished - 2013


  • Frontotemporal dementia
  • Genetic association
  • Parkinson disease
  • TREM2

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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