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

Molecular Neurodegeneration

Owen A Ross⁷  Rosa Rademakers⁷  Dennis W Dickson⁷  Zbigniew K Wszolek^1,13  Neill R Graff-Radford^1,13  Bradley F Boeve³  Kevin B Boylan^1,13  James F Meschia^1,13  Ryan J Uitti^1,13  Nilüfer Ertekin-Taner^1,13  Ronald C Petersen³  Steven G Younkin⁷  Maria Barcikowska⁴  Anna Krygowska-Wajs^1,14  Grzegorz Opala⁹  Magdalena Boczarska-Jedynak⁹  Bruce L Miller¹  Ian R Mackenzie^1,11  Richard Caselli²  Charles L White⁶  David S Knopman³  Keith A Josephs³  Carol Lippa^1,12  Eileen H Bigio⁸  Andrew Kertesz^1,10  Catherine Lomen-Hoerth¹  Kimmo J Hatanpaa⁶  William W Seeley¹  Elizabeth Finger^1,10  Timothy Lynch⁵  Matt Baker⁷  Bianca Mullen⁷  Sruti Rayaprolu⁷ 

[1] Department of Neurology, University of California, San Francisco, CA, USA;Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA;Department of Neurology, Mayo Clinic, Rochester, MN, USA;Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland;Dublin Neurological Institute at the Mater Misericordiae University Hospital, Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Dublin, Ireland;Department of Pathology and Alzheimer's Disease Center, University of Texas Southwestern Medical Center, Dallas, TX, USA;Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA;Cognitive Neurology & Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA;Department of Neurology, Medical University of Silesia, Katowice, Poland;Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada;Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada;Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA;Department of Neurology, Mayo Clinic, Jacksonville, FL, USA;Department of Neurology, Jagiellonian University, Krakow, Poland

关键词: Genetic association;    Parkinson disease;    Frontotemporal dementia;    TREM2;   

Others  :  862313
DOI  :  10.1186/1750-1326-8-19

 received in 2013-06-05, accepted in 2013-06-18,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Rayaprolu et al.; licensee BioMed Central Ltd.

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