However, due to (1) sustained UPR signaling interacting with tau and Aβ (2) the inability of reactive astrocytes and microglia to successfully break down toxic tau and Aβ aggregates, this leads to further tau hyper-phosphorylation resulting in NFT formation, as well as Aβ plaque accumulation – the hallmarks of neurodegeneration seen in AD pathology. Here, MAPT is linked to Alzheimer disease.