Journal
NEUROBIOLOGY OF AGING
Volume 34, Issue 8, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2013.02.016
Keywords
TREM2; Alzheimer's disease; FTLD; neurodegeneration
Categories
Funding
- COLCIENCIAS [111554531651]
- Kronos Science
- National Institute of Neurological Disorders and Stroke [R01 NS059873]
- National Institute on Aging [R01 AG031581, P30 AG19610, AG034504]
- Banner Alzheimer's Foundation
- Johnnie B. Byrd Sr. Alzheimer's Disease Institute
- Medical Research Council
- Intramural Research Program of the National Institutes of Health
- state of Arizona
- National Alzheimer's Coordinating Center (NACC) [U01 AG016976]
- John Hopkins Alzheimer's Disease Research Center (NIA) [AG05146]
- University of California, Los Angeles (NIA) [P50 AG16570]
- Kathleen Price Bryan Brain Bank, Duke University Medical Center (NIA) [AG05128]
- Kathleen Price Bryan Brain Bank, Duke University Medical Center (NINDS) [NS39764]
- Kathleen Price Bryan Brain Bank, Duke University Medical Center (NIMH) [MH60451]
- Kathleen Price Bryan Brain Bank, Duke University Medical Center (Glaxo Smith Kline)
- Massachusetts Alzheimer's Disease Research Center [P50 AG005134]
- University of Michigan (NIH) [P50-AG08671]
- University of Kentucky (NIH) [AG05144]
- St Louis Alzheimer's Disease Research Center (NIH) [P50AG05681]
- University of Washington, Seattle (NIH) [P50 AG05136]
- Boston University Alzheimer's Disease Research Center (NIH) [P30-AG13846]
- Carol Kubilus Sun Health Research Institute Brain Donation Program of Sun City, Arizona (NIA) [P30 AG19610]
- Arizona Alzheimer's Disease Core Center, Arizona Department of Health Services [211002]
- Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]
- Rush University Medical Center, Rush Alzheimer's Disease Center (NIH) [AG10161]
- local NHS trusts
- Newcastle University
- Higher Education Funding Council for England (HEFCE)
- Alzheimer's Research Trust (ART)
- BRACE
- DeNDRoN
- Stichting MS Research
- Brain Net Europe
- Hersenstichting Nederland Breinbrekend Werk
- International Parkinson Fonds
- Internationale Stiching Alzheimer Onderzoek
- North Bristol NHS Trust Research and Innovation Department
Ask authors/readers for more resources
Recent evidence suggests that rare genetic variants within the TREM2 gene are associated with increased risk of Alzheimer's disease. TREM2 mutations are the genetic basis for a condition characterized by polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) and an early-onset dementia syndrome. TREM2 is important in the phagocytosis of apoptotic neuronal cells by microglia in the brain. Loss of function might lead to an impaired clearance and to accumulation of necrotic debris and subsequent neurodegeneration. In this study, we investigated a consanguineous family segregating autosomal recessive behavioral variant FTLD from Antioquia, Colombia. Exome sequencing identified a nonsense mutation in TREM2 (p.Trp198X) segregating with disease. Next, using a cohort of clinically characterized and neuropathologically verified sporadic AD cases and controls, we report replication of the AD risk association at rs75932628 within TREM2 and demonstrate that TREM2 is significantly overexpressed in the brain tissue from AD cases. These data suggest that a mutational burden in TREM2 may serve as a risk factor for neurodegenerative disease in general, and that potentially this class of TREM2 variant carriers with dementia should be considered as having a molecularly distinct form of neurodegenerative disease. (c) 2013 Elsevier Inc. All rights reserved.
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