BDNF and Alzheimer disease: Since acute AD treatment increases phosphorylation of CREB, a critical upstream regulator of BDNF synthesis in a TrkB dependent manner [13], it is tempting to speculate that this ligand-independent TrkB activation is contributing the AD-induced BDNF synthesis in brain [39] which further leads to BDNF-dependent TrkB phosphorylation after prolonged AD administration.