Trem2 Variants and Alzheimer‘s Disease

Abstract

Evaluation of: Guerreiro R, Wojtas A, Brás J et al.TREM2 variants in Alzheimer‘s disease. N. Engl. J. Med. 368(2), 117–127 (2013); Jonsson T, Stefansson H, Steinberg S et al. Variant of TREM2 associated with the risk of Alzheimer‘s disease. N. Engl. J. Med. 368(2), 107–116 (2013). The articles by Guerreiro et al. and Jonsson et al. report the association between a specific exonic variant in the TREM2 gene, a cell surface receptor involved in immune system regulation, and late-onset Alzheimer‘s 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 the TREM2 gene exhibiting an effect size comparable to that of the APOEe4 allele (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.

Keywords:

• Alzheimer‘s disease
• rare variant
• sequencing
• TREM2

Financial & competing interests disclosure

C Reitz was supported by a Paul B Beeson Career Development Award (K23AG034550). G Tosto was supported by Whole Exome Analysis of Early Onset Alzheimer‘s Disease Grant (W81XWH). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

C Reitz was supported by a Paul B Beeson Career Development Award (K23AG034550). G Tosto was supported by Whole Exome Analysis of Early Onset Alzheimer‘s Disease Grant (W81XWH). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.