Neuroinflammation in Alzheimer's Disease: Focus on NLRP1 and NLRP3 Inflammasomes

Alzheimer's disease (AD) is the main cause of dementia worldwide. The definitive diagnosis of AD is clinicopathological and based on the identification of cerebral deposition of Amyloid beta (A beta) plaques and neurofibrillary tangles. However, the link between amyloid cascade and depositions of phosphorylated tau (p-tau) is still missing. In this scenario, inflammasomes might play a relevant role. Experimental models of AD have suggested that A beta accumulation induces, through microglia, activation of the NLRP3 inflammasome. This activation contributes to the dissemination of A beta and p-tau, as well as to hyperphosphorylation of tau. Also, in experimental models, NLPR1 promoted neuronal pyroptosis. There are neither comprehensive neuropathologic characterization nor clinicopathologic studies evaluating the NLRP1 and NLRP3 inflammasomes in subjects with AD. The current mini-review aims to summarize recent and promising findings on the role of NLRP1 and NLRP3 signaling in the pathophysiology of AD. We also sought to highlight the knowledge gap in patients with AD, mainly the lack of clinicopathologic studies on the interaction among inflammasomes, A beta/tau pathology, and cognitive decline.

Automated summary

Alzheimer's disease is the main cause of dementia globally, with the definitive diagnosis based on the identification of cerebral deposition of Amyloid beta plaques and neurofibrillary tangles. Research suggests that inflammasomes may play a significant role in AD, but there is a lack of studies evaluating their role in patients with AD.