beta-Amyloid impairs axonal BDNF retrograde trafficking.
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| Authors |
Poon WW, Blurton-Jones M, Tu CH, Feinberg LM, Chabrier MA, Harris JW, Jeon NL, Cotman CW. |
| Citation Information |
Neurobiol Aging. 2009 Jun 18. [Epub ahead of print] |
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Institute for Brain Aging and Dementia, University of California, Irvine, 1226 Gillespie NRF, Irvine, CA 92697, United States. |
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Abstract |
| The neurotrophin, brain-derived neurotrophic factor (BDNF), is essential for synaptic function, plasticity and neuronal survival. At the axon terminal, when BDNF binds to its receptor, tropomyosin-related kinase B (TrkB), the signal is propagated along the axon to the cell body, via retrograde transport, regulating gene expression and neuronal function. Alzheimer disease (AD) is characterized by early impairments in synaptic function that may result in part from neurotrophin signaling deficits. Growing evidence suggests that soluble beta-amyloid (Abeta) assemblies cause synaptic dysfunction by disrupting both neurotransmitter and neurotrophin signaling. Utilizing a novel microfluidic culture chamber, we demonstrate a BDNF retrograde signaling deficit in AD transgenic mouse neurons (Tg2576) that can be reversed by gamma-secretase inhibitors. Using BDNF-GFP, we show that BDNF-mediated TrkB retrograde trafficking is impaired in Tg2576 axons. Furthermore, Abeta oligomers alone impair BDNF retrograde transport. Thus, Abeta reduces BDNF signaling by impairing axonal transport and this may underlie the synaptic dysfunction observed in AD. |
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