Ibrutinib ↓ LPS-induced DLB and NI by inhibiting NF-κB activation, ↓ pro-inflammatory cytokine levels, normalising redox signalling and its downstream components, including Nrf2, HO-1, and SOD2, and glial cell activation markers, such as IBA-1 and GFAP; ibrutinib ↓ LPS-activated inflammasome activation by targeting NLRP3/P38/Caspase-1 signalling. LPS ↓ the number of dendritic spines and expression of BDNF, and synaptic-related markers, including PSD95, SNAP25, and synaptophysin, were ↑ by ibrutinib in mouse Hippoc. Here, DLG4 is linked to Lewy body dementia.