Familial AD mutants of Aβ precursor protein and presenilin signal, at least in part, through the GSKβ pathway [199] and tau protein undergo GSKβ-mediated phosphorylation, resulting in decreased affinity of binding to the microtubules [200] and consequent neuronal cytoskeleton collapse and axonal transport impairment [201], thus contributing to the AD pathophysiology. The gene discussed is MAPT; the disease is Alzheimer disease.