Cyclooxygenase-2 is critical for the propagation of β-amyloid protein and reducing the glycosylation of tau in Alzheimer’s disease

Alzheimer’s disease(AD)is generally believed to be caused by the production ofβ-amyloid protein(Aβ),and hyperphosphorylation of tau,which are deposited inβ-amyloid plaques(APs)and neurofibrillary tangles(NFTs),respectively.However,the inherent reasons for their propagation and deposition remain unknown.In light of our prior works,magnesium(Mg2+)deficiency is critical for the onset of AD.1 In addition,the restoration of Mg2+in the brain reduces neuroinflammation by suppressing the expression of interleukin(IL)-1β,1 which decreases Aβoverload in an APH-1α/1β-dependent mechanism.2 In this regard,inflammation is the target of Mg2+in the treatment of AD.In addition to IL-1β,a powerful inflammatory inducer,cyclooxygenase-2(COX-2),has also been reported to be inhibited by the addition of Mg2+.3 We thereby extended our prior works to COX-2.Analyses of the underlying mechanisms elucidated the role of COX-2 in spreading Aβdeposits in APs to the cerebellum.This was probably caused by the formation of hetero-oligomers between COX-2 and Aβ,which have been shown to accelerate the aggregation and deposition of Aβin APs.4 Moreover,the induction of COX-2 decreased the glycosylation of tau,which has been shown to result in the phosphorylation of tau in different animal models.In this scenario,the status of tau phosphorylation is critical for the development and progression of AD.5 Therefore,COX-2 appears to be a potential therapeutic target for AD.