摘要：

Evaluation of: Guerreiro R, Wojtas A, Brás Jet al.TREM2variants in Alzheimers disease.N. Engl. J. Med.368(2), 117–127 (2013); Jonsson T, Stefansson H, Steinberg Set al.Variant ofTREM2associated with the risk of Alzheimers disease.N. Engl. J. Med.368(2), 107–116 (2013).The articles by Guerreiroet al.and Jonsson et al. report the association between a specific exonic variant in theTREM2gene, a cell surface receptor involved in immune system regulation, and late-onset Alzheimers disease (AD). The observations of these studies are relevant as they further disentangle the genetic causes underlying AD by identifying a disease-associated rare variant in theTREM2gene exhibiting an effect size comparable to that of theAPOEe4allele (i.e., increasing the risk approximately twofold) thereby strengthening the link between AD and the immune system. All other AD-associated genes described to date have shown smaller effect sizes with increases in risk of 10–20%. The two articles also underline the role of rare variants in this complex disease and the importance of sequencing analyses for detecting these, while commonly used genome-wide association studies are typically designed to screen the genome and identify common variants.

展开