Rare variants in the TREM2 (triggering receptor expressed on myeloid cells 2) gene are associated with an increased risk of late-onset Alzheimer disease (AD), report two independent groups of researchers in The New England Journal of Medicine.“[This discovery] points very specifically to a potential metabolic pathway that you could intervene in to change the course of Alzheimer's disease,” says William Thies, chief medical and scientific officer of the Alzheimer's Association (New York Times, 14 Nov 2012).

As part of a large international collaboration, a team led by John Hardy focused in on the TREM2 gene, following their earlier discovery that homozygous loss-of-function mutations in TREM2 were associated with an unusual early-onset form of dementia in Turkish patients.“We had found the same mutations in some of our Alzheimer's cases, only heterozygous rather than homozygous,” Hardy explains. As part of the deCODE project, Kari Stefansson and colleagues took a different approach, channelling their efforts into analysing whole-genome sequences in the genetically homogeneous Icelandic population.