On the other hand, the formation and accumulation of Aβ and Tau, including their oligomers, as well as ER stress, PrPC, O-GlcNAcylation, oxidative stress, insulin/IGF resistance and glial malfunction are all involved in AD development, and all of them are directly and/or indirectly related to each other in AD pathogenesis and advancement, thereby creating a vicious cycle of AD progression in the brain. This evidence concerns the gene PRNP and Alzheimer disease.