Professor Salinas research provides new insights for promoting synapse repair in Alzheimer's disease

Alzheimer’s disease, the most common form of dementia, is caused by the degeneration of synapses, special connections between nerve cells, resulting in memory loss. Wnts (proteins released from cells in the nervous system) are critical to synapse development and maintenance in the adult brain, yet recent studies have highlighted a mutation in the Wnt receptor, variant LRP6, which results in reduced Wnt signalling and increases the risk of developing Alzheimer’s disease.

Salinas and her team created a novel mouse model that carries the variant LRP6 using genome editing. Her study identified that carrying this variant of LRP6 enhances synaptic defects and synapse loss during ageing and increases synapse degeneration in Alzheimer’s disease. These changes in connectivity could result in a detrimental effect on cognitive function in human carriers of the LRP6 variant. The study also identified that the mutant receptor does not initiate Wnt signalling or promote synapse formation in response to Wnt proteins.

The findings from Salinas’s research highlight a significant step forward in the field of neurodegeneration by showcasing a role for Wnt signalling in synapse integrity in the brain. The study also provides new insights into potential targets for promoting synapse repair/recovery in Alzheimer’s disease.

“We are thrilled that our work focused on the biological impact on a variant of a key Wnt receptors has been well received by experts in the field.  Our work uncovered new mechanistic insights into how synapses are loss in AD and that defects in Wnt function contributes to synaptic changes in the Alzheimer’s brain. They also provide the bases for developing new therapies for restoring brain function in Alzheimer’s disease” said Professor Patricia C. Salinas

The research, published in Science Advances, was funded by the MRC, Alzheimer’s Research UK and the Wellcome Trust.

Resources:

• https://salinaslabucl.co.uk/
• Science Advances
• MRC 
• Alzheimer’s Research UK 
• The Wellcome Trust
• Alzheimer’s Society