Effects of rs2234246 with microRNA-138-5p on TREM1 mRNA expression and right hippocampal atrophy in Alzheimer’s disease

Alzheimer’s disease (AD) is a major neurodegenerative disorder with amyloid beta deposition in senile plaques and phosphorylated tau in neurofibrillary tangles pathologically. Triggering receptor expressed on myeloid cells 1 (TREM1) is one of the microglial proteins, and recently, rs2234246, located in the 3’-untranslated region (UTR) of TREM1 , was reported to be associated with amyloid beta deposition in AD patients and TREM1 expression. In this study, rs2234246 in TREM1 , microRNA (miR)-138-5p that binds TREM1 seed sequence, and the hippocampal atrophy of AD patients were investigated. Three studies, including SNP functional analysis (92 controls), TREM1 protein, mRNA, and miR-138-5p expression study (40 control and 40 AD patients), and brain MRI analysis (181 control and 50 AD patients), were performed. The genotyping of rs2234246 and measurement of TREM1 mRNA and miR-138-5p expressions were conducted by qPCR methods. A dual luciferase reporter assay was used to investigate the difference in miR-138-5p binding to the seed sequence in each allele of rs2234246. Atrophy of the hippocampi was assessed on magnetic resonance imaging (MRI). The expression of the membrane form ( mbTREM1 ), but not the soluble form ( TREM1sv ) of TREMI was significantly regulated by rs2234246. The dual luciferase reporter assay showed that miR-138-5p binds on the seed sequence when the rs2234246 genotype is A. Moreover, rs2234246 ^A was associated with progression of right hippocampal atrophy in AD patients. In conclusion, TREM1 and miR-138-5p may be the key factors in the inflammatory process involved in the pathogenesis of AD.