Another crucial mechanism through which the presence of Aβ induced oxidative stress is neuroinflammation
[52]. Neuroinflammation is considered as an immunological response characterized by the activation of glial cells and the production of inflammatory mediators
[53]. Numerous studies revealed a strong correlation between neuroinflammation and AD pathology
[54][55][56]; thus, inflammatory cytokines have been reported to increase in the progression of mild cognitive impairment to overt AD
[57]. A microarray study of Cribbs and collaborators performed on young, aged, and AD cases demonstrated an upregulation of the innate immune response in aging brains and a slight increase in related genes
[58], suggesting that inflammation has a role in the preclinical stages of AD. In this context, microglia play a leading role in neuroinflammation
[53]. Aβ can bind different microglial receptors, resulting in the production not only of inflammatory cytokines and chemokines
[58] but also of a large amount of oxygen free radicals (
•OH and O₂
•)
[59], nitric oxide (
•NO)
[60], and tumour necrosis factor (TNF) α
[61]. The NLR family pyrin domain containing 3 (NLRP3) inflammasome is a recently found cytoplasmic protein complex involved in neuroinflammation and innate immune response
[62]. Recent studies demonstrated that Aβ induce NLRP3 activation in microglia and astrocytes. This event results in the production of caspase 1 and induces the release of cytokines such as IL1β and IL-18, resulting in irreversible damage. On the other hand, the inhibition of NLRP3 inflammasome inhibits Aβ deposition and had a neuroprotective effect in a transgenic AD mouse model
[63][64][65][66]. Thus, all these findings suggest that Aβ is a crucial factor in AD associated inflammation and oxidative stress.