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.
