Tau can be phosphorylated by several protein kinases. Phosphorylation by Tau
protein kinase II at Serine 404 is primarily responsible for the functional loss
of Tau-mediated tubulin polymerization. In addition, phosphorylation of microtubule-
associated Tau results in the dissociation of Tau from the microtubules
and tubulin depolymerization. Serine 412 of Tau is modified by Tau protein
kinase I/glycogen synthase kinase-3β (TPKI/GSK-3β) to disrupt neuronal
metabolism in anatomical areas vulnerable to Alzheimer’s disease. TPKI/
GSK-3β is expressed primarily in neurons and especially in neurites early in
development, whereafter the distribution is concentrated mostly in the cell
soma and the proximal neurite region.