Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) plaques and neuroinflammation. The NLRP3 inflammasome, a key sensor of microbial components and sterile danger signals, plays a significant role in the innate immune response to Aβ. This study demonstrates that NLRP3 activation contributes to AD pathology by driving neuroinflammation and exacerbating Aβ accumulation. In APP/PS1 mice, which model familial AD, NLRP3 deficiency significantly reduces Aβ deposition, improves memory function, and alters microglial phenotype towards an M2-like state, which is associated with enhanced Aβ clearance. The study also shows that NLRP3 deficiency reduces caspase-1 and IL-1β activation, leading to decreased neuroinflammation and improved synaptic plasticity. These findings highlight the critical role of the NLRP3/caspase-1 axis in AD pathogenesis and suggest that targeting the NLRP3 inflammasome could be a promising therapeutic strategy for AD. The results indicate that chronic Aβ deposition activates microglia, leading to persistent inflammation and neuronal dysfunction. Inflammasome activation, particularly through NLRP3, enhances this inflammatory response, contributing to the progression of AD. By reducing NLRP3 activity, the study demonstrates a potential therapeutic approach that could mitigate the harmful effects of chronic inflammation in AD. The findings provide a deeper understanding of the mechanisms underlying AD and offer new avenues for the development of treatments targeting the inflammasome pathway.Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) plaques and neuroinflammation. The NLRP3 inflammasome, a key sensor of microbial components and sterile danger signals, plays a significant role in the innate immune response to Aβ. This study demonstrates that NLRP3 activation contributes to AD pathology by driving neuroinflammation and exacerbating Aβ accumulation. In APP/PS1 mice, which model familial AD, NLRP3 deficiency significantly reduces Aβ deposition, improves memory function, and alters microglial phenotype towards an M2-like state, which is associated with enhanced Aβ clearance. The study also shows that NLRP3 deficiency reduces caspase-1 and IL-1β activation, leading to decreased neuroinflammation and improved synaptic plasticity. These findings highlight the critical role of the NLRP3/caspase-1 axis in AD pathogenesis and suggest that targeting the NLRP3 inflammasome could be a promising therapeutic strategy for AD. The results indicate that chronic Aβ deposition activates microglia, leading to persistent inflammation and neuronal dysfunction. Inflammasome activation, particularly through NLRP3, enhances this inflammatory response, contributing to the progression of AD. By reducing NLRP3 activity, the study demonstrates a potential therapeutic approach that could mitigate the harmful effects of chronic inflammation in AD. The findings provide a deeper understanding of the mechanisms underlying AD and offer new avenues for the development of treatments targeting the inflammasome pathway.