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Updated: Jun 22, 2026
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Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons
Published on: October 30, 2018
β-Amyloid impairs axonal BDNF retrograde trafficking.
Wayne W Poon1, Mathew Blurton-Jones, Christina H Tu
1Institute for Brain Aging and Dementia, University of California, Irvine, 1226 Gillespie NRF, Irvine, CA 92697, United States. wpoon@uci.edu
Neurobiology of Aging
|June 23, 2009
Summary
Alzheimer disease (AD) impairs brain-derived neurotrophic factor (BDNF) retrograde signaling by disrupting axonal transport of its receptor, tropomyosin-related kinase B (TrkB). This deficit, caused by amyloid-beta (Aβ) oligomers, may underlie synaptic dysfunction in AD.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Brain-derived neurotrophic factor (BDNF) is crucial for neuronal survival, plasticity, and synaptic function.
- Alzheimer disease (AD) is linked to impaired neurotrophin signaling and synaptic dysfunction.
- Soluble amyloid-beta (Aβ) assemblies are implicated in disrupting neurotrophin signaling.
Purpose of the Study:
- To investigate the impact of AD on BDNF retrograde signaling.
- To determine if Aβ oligomers disrupt BDNF retrograde transport.
- To explore potential therapeutic interventions for AD-related signaling deficits.
Main Methods:
- Utilized a novel microfluidic culture chamber for neuronal studies.
- Employed BDNF-green fluorescent protein (GFP) to track BDNF-mediated receptor trafficking.
- Examined neurons from AD transgenic mouse models (Tg2576).
Main Results:
- Demonstrated a deficit in BDNF retrograde signaling in AD transgenic mouse neurons.
- Showed that γ-secretase inhibitors can reverse this signaling deficit.
- Confirmed impaired BDNF-mediated tropomyosin-related kinase B (TrkB) retrograde trafficking in AD axons.
- Established that Aβ oligomers alone impair BDNF retrograde transport.
Conclusions:
- Aβ reduces BDNF signaling by impairing axonal transport.
- Impaired BDNF retrograde signaling and axonal transport contribute to synaptic dysfunction in AD.
- γ-secretase inhibitors show potential for restoring BDNF signaling in AD.
