Comments to the "Letter to the Editor" for the manuscript titled "Increased expression of inflammasome signaling genes and proteins in selective brain regions in the intermediate stage of Alzheimer's disease".

Beta amyloid diffuse plaques, neurofibrillary tangles and neuritic plaques, are increased in densities at the intermediate stage of Alzheimer's neuropathological change. These pathological changes releasing Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs). These molecules are sensed by pattern recognition receptors (PRRs) and trigger intracellular responses. One response is the activation of the inflammasome sensors NLRP1, NLRP3, and AIM2 to oligomerize with ASC speck to form the inflammasome complex and initiate the downstream signaling of GSDMD mediated pyroptosis. Another response is the increase in genes to manufacture proinflammatory cytokines, the inflammasome formation activates the cleavage of the proinflammatory cytokines to the activated forms, which are secreted into the extracellular environment and recruit a widespread inflammation.