Alzheimer’s disease (AD), recognized as the most common neurodegenerative disorder,
is clinically characterized by the presence of extracellular beta-amyloid (Aβ) plaques and by intracellular
neurofibrillary tau tangles, accompanied by glial activation and neuroinflammation. Increasing
evidence suggests that self-misfolded proteins stimulate an immune response mediated by
glial cells, inducing the release of inflammatory mediators and the recruitment of peripheral macrophages
into the brain, which in turn aggravate AD pathology.
The present review aims to update the current knowledge on the role of autoimmunity and neuroinflammation
in the pathogenesis of the disease, indicating a new target for therapeutic intervention.
We mainly focused on the NLRP3 microglial inflammasome as a critical factor in stimulating innate
immune responses, thus sustaining chronic inflammation. Additionally, we discussed the involvement
of the NLRP3 inflammasome in the gut-brain axis. Direct targeting of the NLRP3 inflammasome
and the associated receptors could be a potential pharmacological strategy since its
inhibition would selectively reduce AD neuroinflammation.