Variant of TREM2 associated with the risk of Alzheimer's disease.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Jonsson, Palmi V
Levey, Allan I
Lah, James J
Andreassen, Ole A
Ikram, M Arfan
van Duijn, Cornelia M
MetadataShow full item record
CitationN. Engl. J. Med. 2013, 368(2):107-16
AbstractBACKGROUND: Sequence variants, including the ε4 allele of apolipoprotein E, have been associated with the risk of the common late-onset form of Alzheimer's disease. Few rare variants affecting the risk of late-onset Alzheimer's disease have been found. METHODS: We obtained the genome sequences of 2261 Icelanders and identified sequence variants that were likely to affect protein function. We imputed these variants into the genomes of patients with Alzheimer's disease and control participants and then tested for an association with Alzheimer's disease. We performed replication tests using case-control series from the United States, Norway, The Netherlands, and Germany. We also tested for a genetic association with cognitive function in a population of unaffected elderly persons. RESULTS: A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P=3.42×10(-10)). The mutation had a frequency of 0.46% in controls 85 years of age or older. We observed the association in additional sample sets (odds ratio, 2.90; 95% CI, 2.16 to 3.91; P=2.1×10(-12) in combined discovery and replication samples). We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer's disease had poorer cognitive function than noncarriers (P=0.003). CONCLUSIONS: Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes. (Funded by the National Institute on Aging and others.).
DescriptionTo access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.
- TREM2 variants in Alzheimer's disease.
- Authors: Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, Hazrati L, Collinge J, Pocock J, Lashley T, Williams J, Lambert JC, Amouyel P, Goate A, Rademakers R, Morgan K, Powell J, St George-Hyslop P, Singleton A, Hardy J, Alzheimer Genetic Analysis Group.
- Issue date: 2013 Jan 10
- Association study of TREM2 polymorphism rs75932628 with late-onset Alzheimer's disease in Chinese Han population.
- Authors: Ma J, Zhou Y, Xu J, Liu X, Wang Y, Deng Y, Wang G, Xu W, Ren R, Liu X, Zhang Y, Wang C, Tang H, Chen S
- Issue date: 2014 Oct
- TREM2 R47H variant as a risk factor for early-onset Alzheimer's disease.
- Authors: Pottier C, Wallon D, Rousseau S, Rovelet-Lecrux A, Richard AC, Rollin-Sillaire A, Frebourg T, Campion D, Hannequin D
- Issue date: 2013
- More evidence for association of a rare TREM2 mutation (R47H) with Alzheimer's disease risk.
- Authors: Rosenthal SL, Bamne MN, Wang X, Berman S, Snitz BE, Klunk WE, Sweet RA, Demirci FY, Lopez OL, Kamboh MI
- Issue date: 2015 Aug
- Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study.
- Authors: Gonzalez Murcia JD, Schmutz C, Munger C, Perkes A, Gustin A, Peterson M, Ebbert MT, Norton MC, Tschanz JT, Munger RG, Corcoran CD, Kauwe JS
- Issue date: 2013 Dec