MAPT and early-onset autosomal dominant Alzheimer disease: In Alzheimer's disease, tau is highly phosphorylated, and many of the tau phosphorylation sites targeted by glycogen synthase kinase-3 (GSK-3), the primary candidate kinase for tau phosphorylation, are also phosphorylated in insoluble tau isolated from Alzheimer brain (Avila et al., 2012; Hanger et al., 2007, 2009).