NGF also stimulates tau ubiquitination through K63-linked poly-Ub in neuronal cell differentiation (25), which implies the possibility of the downregulation of the NGF signaling pathway in AD pathogenesis by impairing normal tau ubiquitination, as the decrease of NGF in the cortex and hippocampus mediates cholinergic neuron degeneration in the basal forebrain at disease onset. The gene discussed is MAPT; the disease is Alzheimer disease.