Disease Associated Microglial TLR4-Lyn kinase is a critical regulator of neuroinflammation, Aß phagocytosis, neuronal damage and cell survival in a 5XFAD mouse model.

Disease-Associated Microglia (DAM) are a focus in Alzheimer's disease (AD) research due to their central involvement in the response to amyloid-beta plaques. Microglial Toll-like receptor 4 (TLR4) is instrumental in the binding of fibrillary amyloid proteins, while Lyn kinase (Lyn) is a member of the Src family of non-receptor tyrosine kinases involved in immune signaling. Increased expression of protective Syk kinase was observed, enhanced microglial Aß phagocytosis, decreased neuronal dystrophy, and a further increase in the cell survival signaling and protective DAM population was noted. Lyn can be activated in response to TLR4 stimulation, leading to phosphorylation of various substrates and modulation of inflammatory and phagocytosis signaling pathways. Overall design: WT, APP, 5xFAD and 5xFAD x LynKO animal groups were used for spatial transcriptomics experiment. Each brain slices were assayed with Tmem119 (microglia) and GFAP (astrocyte) markers using 6 ROIs each. In our study we have analysed the microglial gene expressions in the WT, 5xFAD and 5xFAD x LynKO groups.