TREM2 variants in Alzheimer's disease

David Mann, Rita Guerreiro, Aleksandra Wojtas, Jose Bras, Minerva Carrasquillo, Ekaterina Rogaeva, Elisa Majounie, Carlos Cruchaga, Celeste Sassi, John S K Kauwe, Steven Younkin, Lilinaz Hazrati, John Collinge, Jennifer Pocock, Tammaryn Lashley, Julie Williams, Jean Charles Lambert, Philippe Amouyel, Alison Goate, Rosa RademakersKevin Morgan, John Powell, Peter St George-Hyslop, Andrew Singleton, John Hardy

    Research output: Contribution to journalArticlepeer-review


    Background: Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia. Methods: We used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease. We genotyped the R47H variant in an additional 1887 cases and 4061 controls. We then assayed the expression of TREM2 across different regions of the human brain and identified genes that are differentially expressed in a mouse model of Alzheimer's disease and in control mice. Results: We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set (P = 0.02). There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5 variant alleles in 1107 controls (P
    Original languageEnglish
    Pages (from-to)117-127
    Number of pages10
    JournalNew England Journal Of Medicine
    Issue number2
    Publication statusPublished - 10 Jan 2013


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