Even though the tau phosphorylation at specific sites is associated with aggregated tau burdens and is used in diagnostic and immunohistological confirmation of tauopathies [153,154,155], the causative effect of PTMs on tau misfolding and generating tau seeds competent to spread the tau pathology is debated in light of recent data that show seeding activity even in the absence of phosphorylated tau deposits [40,156,157,158]. This evidence concerns the gene MAPT and tauopathy.