MAPT and Cognitive impairment: Phosphorylated tau aggregates into paired helical filaments and forms neurofibrillary tangles (NFTs), the production of which is tightly correlated with the degree of cognitive impairment.12, 13 An increasing number of researchers believe that soluble hyperphosphorylated tau also directly damages microtubules.14 Tau protein has ~80 phosphorylation sites distributed in all four domains, and these sites are under the control of several kinases, such as PKA, GSK-3β and CDK-5.