Alzheimer's disease (AD) is the primary cause of dementia in elderly individuals, characterized
by progressive memory loss, cognitive decline, and impaired daily functioning. Pathologically,
AD is associated with the accumulation of amyloid-β (Aβ) plaques, tau tangles, mitochondrial
dysfunction, and chronic neuroinflammation. The activation of the NOD-like receptor pyrin domain-
containing 3 (NLRP3) inflammasome by Aβ clusters triggers microglial activation, leading to
a cascade of inflammatory responses. Similarly, tau tangles stimulate neuronal and glial cells, further
amplifying NLRP3 activation and perpetuating a cycle of chronic inflammation. Mitochondrial
dysfunction exacerbates this process by increasing oxidative stress and inflammasome activation.
Additionally, purinergic receptor P2X7 (P2X7R) activation in microglia plays a crucial role in initiating
neuroinflammation, making it a potential therapeutic target. Despite extensive research, current
AD therapies remain symptomatic rather than disease-modifying. Targeting the NLRP3 inflammasome
offers a promising strategy for mitigating AD progression. Various small-molecule inhibitors,
monoclonal antibodies, and repurposed drugs have been explored to inhibit NLRP3 activation
and its downstream signaling pathways. Preclinical studies suggest that NLRP3 inhibitors effectively
reduce Aβ- and tau-induced neuroinflammation while improving mitochondrial function and
overall neuronal survival. This review summarizes NLRP3 inflammasome priming, activation, and
the therapeutic potential of its inhibitors in AD, highlighting challenges such as tau pathology, biomarker
limitations, and treatment optimization. While NLRP3 remains a promising target, most inhibitors
are in the early stages with uncertain long-term efficacy and BBB penetration. Future research
should explore genetic variability, sex differences, and alternative approaches to enhance
neuroprotective strategies.