Amyloid-beta, BDNF, and the mechanism of neurodegeneration in alzheimer's disease

Abstract

The accumulation of amyloid-β is widely considered the primary neurotoxic insult leading to Alzheimer's disease. Although the precise mechanism of this toxicity is not well understood, amyloid-ß-induced downregulation of brain- derived neurotrophic factor may be one of the most important contributors to amyloid-ß toxicity. Brain-derived neurotrophic factor has diverse neurotrophic effects on the nervous system, including promoting synaptic plasticity and neurogenesis, and it is essential for cognition and memory. Early in the progression of Alzheimer's disease, prior to significant plaque and tangle deposition, declining brain-derived neurotrophic factor expression induced by amyloid-ß is associated with mounting impairments in cognition and memory. A variety of approaches have demonstrated that increasing brain-derived neurotrophic factor levels improves learning and memory, highlighting the possibility that therapeutically restoring brain-derived neurotrophic factor levels may prevent or reverse the memory impairments and cognitive decline seen in Alzheimer's disease.