MAPT and neurodegenerative disease: Notwithstanding, in aging (Hof et al., 1996) and neurodegenerative diseases (i.e., AD, Down syndrome, and tauopathies) an excessive phosphorylation of tau causes its self-aggregation (Alonso et al., 2001) in straight and paired-helical filaments which subsequently form the so called neurofibrillary tangles (NFT).