Della et al. (2002) found that the addition of purified non-ubiquitylated recombinant Tau to the 20S proteasome resulted in the degradation of Tau proteins, indicating a UPS-dependent degradation of Tau. Inhibition of proteasome function in 3xTgAD mice was found to lead to pathological accumulation of Tau (Tseng et al., 2008). In addition, changes in the co-localization of excess p-Tau with UbK48 were found in hippocampal neurons of AD model mice, and both led to cellular inflammation and induced apoptosis in neuronal cells (Li et al., 2024). This evidence concerns the gene MAPT and Alzheimer disease.