Related Experiment Video
Updated: Feb 20, 2026
Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons
Published on: October 30, 2018
Amyloid β synaptotoxicity is Wnt-PCP dependent and blocked by fasudil
Katherine J Sellers1, Christina Elliott1, Joshua Jackson2
1King's College London, Maurice Wohl Clinical Neuroscience Institute, London, UK.
Introduction:
Synapse loss is the structural correlate of the cognitive decline indicative of dementia. In the brains of Alzheimer's disease sufferers, amyloid β (Aβ) peptides aggregate to form senile plaques but as soluble peptides are toxic to synapses. We previously demonstrated that Aβ induces Dickkopf-1 (Dkk1), which in turn activates the Wnt-planar cell polarity (Wnt-PCP) pathway to drive tau pathology and neuronal death.
Methods:
We compared the effects of Aβ and of Dkk1 on synapse morphology and memory impairment while inhibiting or silencing key elements of the Wnt-PCP pathway.
Results:
We demonstrate that Aβ synaptotoxicity is also Dkk1 and Wnt-PCP dependent, mediated by the arm of Wnt-PCP regulating actin cytoskeletal dynamics via Daam1, RhoA and ROCK, and can be blocked by the drug fasudil.
Discussion:
Our data add to the importance of aberrant Wnt signaling in Alzheimer's disease neuropathology and indicate that fasudil could be repurposed as a treatment for the disease.
More Related Videos
04:41Preparation of Oligomeric β-amyloid1-42 and Induction of Synaptic Plasticity Impairment on Hippocampal Slices
Published on: July 14, 2010
09:52Modified Roller Tube Method for Precisely Localized and Repetitive Intermittent Imaging During Long-term Culture of Brain Slices in an Enclosed System
Published on: December 28, 2017
Related Concept Videos
03:03Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
03:03Amyloid Fibrils