TREM2 analysis and increased risk of Alzheimer's disease.

Important insights into the pathogenic mechanism of Alzheimer's disease (AD) have arisen from the identification of genetic risk factors. Recently, a variant in the TREM2 gene (rs75932628), causing a C-to-T base-pair change that results in the substitution of histidine for arginine at amino acid position 47 (R47H) in the TREM2 protein, has been associated with an increased risk of AD. We, therefore, genotyped samples from a cohort of 474 AD patients and 608 healthy controls, from the northwest region of the UK, using allelic discrimination assays, to replicate the results of the previous studies. We show a significant association of the T allele of the rs75932628 variant of TREM2 with AD (allelic odds ratio 11.08, 95% confidence interval 2.55-48.09, and Yates' corrected p value = 0.000146). TREM2 is an innate immune receptor that regulates microglial cytokine production and phagocytosis, implying that dysregulation of these processes may be involved in AD pathology, with implications for disease management.