Increasing evidence suggests that synaptic dysfunction is a key pathophysiological hallmark in neurodegenerative disorders, including Alzheimer’s disease. Understanding the role of brain-derived neurotrophic factor (BDNF) in synaptic plasticity and synaptogenesis, the impact of the BDNF Val66Met polymorphism in Alzheimer’s disease-relevant endophenotypes – including episodic memory and hippocampal volume – and the technological progress in measuring synaptic changes in humans all pave the way for a ‘synaptic repair’ therapy for neurodegenerative diseases that targets pathophysiology rather than pathogenesis. This review article discusses key issues in translating BDNF biology into synaptic repair therapies.
Lu B, Nagappan G, Guan X, Nathan PJ, Wren P: BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nature Rev. Neurosci. [Epub ahead of print, May 15, 2013, doi: 10.1038/nrn3505].