Because of the technical limitations, the sequential action of different types of unconventional ubiquitin-specific linkages, such as K6- and K11-linked polyubiquitin, and their hybrid ubiquitination with K48 or K63 on tau fibrils has not been explored well to better understand the temporal consequences of these on tau degradation in AD and tauopathy. This evidence concerns the gene MAPT and tauopathy.