Investigating the Regulatory Effects of Probiotics on TREM2 and its Interacting Partners in Mouse Model of Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative condition that includes β-amyloid plaques, tau tangles, oxidative stress, and neuroinflammation. Current treatments provide limited results, demanding novel therapeutic approaches. Despite substantial studies, viable treatments for Alzheimer's disease remain elusive. Targeting certain pathways, such as triggering receptors expressed on Myeloid Cell 2 (TREM2), could provide novel treatment options. This study aims to evaluate the therapeutic potential of probiotics in altering TREM2 expression and activity in AlCl3-induced AD mice models. Specific goals include evaluating the efficacy of oral probiotics in restoring TREM2 expression, measuring mRNA alterations using RT-PCR, and identifying protein-protein networks linked with TREM2 in AD. AD mouse models were induced with AlCl3, and probiotics (LA85, LRa80, BLa80, BBi32) and Donepezil was given orally for 28 days. Histopathology analysis, gene expression analysis, and transcriptional analysis using conventional and real-time quantitative PCR were performed. In- silico analysis with STRING version 12 revealed connections between TREM2 and related proteins. Histopathological studies demonstrated that probiotic-treated groups had higher neuronal number and density. Gene expression analysis revealed a substantial decrease in TREM2 expression in probiotic-treated groups (0.76±0.11) as compared to AlCl3-induced (1.83±0.05) AD mice. In-silico research identified a complicated network involving TREM2, APOE, and CLU, suggesting possible therapeutic targets. The data indicate that probiotics may improve AD pathogenesis via TREM2 modulation, providing a new treatment pathway. Future research should concentrate on personalized probiotic therapies, long-term efficacy assessments, and the molecular mechanisms that underpin probiotic-mediated TREM2 regulation. Exploring synergistic effects with existing medications and focusing on specific pathways in AD etiology could improve therapeutic outcomes.