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NIH-supported international teams identify rare Alzheimer's disease risk gene variant

Two international teams of researchers, with NIH scientists and support, have separately identified a rare variation in the TREM2 gene as a moderate risk factor for late-onset Alzheimer’s disease. TREM2 is a gene involved in inflammation and immune response, and this discovery provides an important clue for researchers seeking a better understanding of the Alzheimer’s disease process. Researchers have hypothesized for many years that a rare genetic variant can confer moderate risk for disease. These are the first studies to identify such a variant related to Alzheimer’s disease.

The first group was led by John Hardy, Ph.D., of University College London (UCL) Institute of Neurology and at NIH by Andrew Singleton, Ph.D., of the NIA. The second team was led by deCODE Genetics, Reykjavik, Iceland, whose work was supported in part by NIH.

The approach taken to find this gene variant suggests that a similar research strategy should help identify additional variants of this type. The researchers in the UCL group used genome, exome and Sanger sequencing to analyze the genetic variability of TREM2 in 988 people with Alzheimer’s disease and 1,004 normal participants. They performed a meta-analysis of genome-wide association studies for Alzheimer’s and tested brain tissues from deceased Alzheimer’s patients. They also compared TREM2 gene expression in a transgenic mouse model of the disease.

The deCODE group obtained genome sequences from 2,261 Icelanders and identified sequence variations considered likely to affect protein function. They replicated their finding in a cohort from the NIA-supported Alzheimer’s Disease Research Center at Emory University, Atlanta, as well as in population groups in Norway, the Netherlands, and Germany.


Guerriero R, et al. TREM2 Variants in Alzheimer’s Disease. New England Journal of Medicine. Published online, November 14, 2012.

Jonsson T, et al. Variant of TREM2 Associated with the Risk of Alzheimer’s Disease New England Journal of Medicine. Published online, November 14, 2012.