A Novel Rare Homozygous R47C Variant in TREM2 with Frontal Variant Alzheimer's Disease.

Triggering Receptor expressed on Myeloid cells 2 (TREM2) mutations can cause Nasu-Hakola disease, a rare form of dementia, and are also linked to an increased risk of Alzheimer's disease (AD) and frontotemporal dementia (FTD). The TREM2 receptor plays a role in microglial cell function, including response to injury and amyloid beta pathology in the brain. Variants in TREM2, particularly in exon 2, can disrupt its function, contributing to AD pathology, such as accumulation of amyloid beta plaques and tau tangles. In this study, we conducted screening of exon 2 in TREM2 to identify mutations in a carefully characterized cohort comprising individuals with AD, FTD, and mild cognitive impairment (MCI) from South India. We report the identification of a homozygous p.R47C variant (rs753325601) in a case diagnosed with frontal variant AD. Our finding reinforces the correlation between TREM2 genetic variations and the manifestation of atypical AD phenotypes, highlighting the significance of TREM2 mediated pathogenic mechanisms in modulating disease presentation.