Brain-derived neurotrophic factor (BDNF) is a critical molecule for learning and memory. Brain BDNF levels correlate with cognitive status. BDNF is downregulated in Alzheimer’s disease, in age-related cognitive impairment and in a variety of other neurodegenerative and psychiatric disorders exhibiting cognitive deficits. BDNF is downregulated in the Alzheimer’s disease brain by soluble, aggregated amyloid-β, acting via a pathway involving the transcription factor cAMP response element binding protein, which activates BDNF transcript IV. The complete pathway by which BDNF is downregulated is still unclear, and the diagnostic and therapeutic use of BDNF in neurodegenerative disease has not yet been exploited.