Microbiome-Microglia interaction in Alzheimer's disease

Alzheimer’s disease (AD) affects over 55 million people worldwide, with no effective treatments currently available. Understanding early-stage mechanisms of the disease is critical to developing new therapeutic approaches. Microglial cells, key regulators of amyloid-beta (Aβ) clearance and neuroinflammation, are implicated in the progression of AD. Emerging evidence suggests that the gut microbiota, through its influence on microglial function, may play a pivotal role in AD pathogenesis. However, the precise regulatory mechanisms of the gut-microbiota-brain axis in AD remain unexplored.The MiMi-AD project, aims to elucidate the role of gut microbiota in modulating microglial activity across AD progression stages, using the Tg2576 mouse model of AD. Specifically, the project will investigate whether exercise-induced alterations in gut microbiota can prime microglial cells to promote Aβ clearance, delay cognitive decline, and reduce neuroinflammation. The research will employ cutting-edge transcriptomics, metabolomics, and microbiota analysis to explore these dynamic interactions, along with in vivo and in vitro studies to identify targetable microbial metabolites.The outcomes of this research could identify novel gut-brain axis pathways, providing a foundation for therapeutic strategies aimed at delaying the onset of AD. Through interdisciplinary collaboration, this project aligns with European and global priorities in promoting healthy aging, offering potential benefits for individuals at risk of developing AD.