Saving synapses in Alzheimer’s disease

Research project: The role of Wnt signalling in synapse maturation in neurons derived from human iPSCs

Lead Investigator: Professor Patricia Salinas

  • Institution: University College London
  • Grant type: PhD studentship
  • Duration: 24 months 
  • Amount: £47,692

Project summary

Professor Salinas aims to understand the role of specific proteins called Wnts in maintaining the connections between cells known as synapses. Synapses are lost in Alzheimer’s disease and the research team want to understand why that is and how it could be prevented. 

The background

Nerve cells in the brain are connected across gaps called synapses. The nerve cells need these synapses to function correctly. Researchers believe that the breakdown and loss of synapses is one of the earliest changes in Alzheimer's disease and could lead to the death of these vital cells. 

Large, toxic clumps of a protein called amyloid are found in the brain in people with Alzheimer's disease. Researchers believe that something within the plaques could be toxic to the synapses. Synapses are maintained by proteins known as Wnts. Much of what we know about the role of synapses in dementia is through animal studies but we know relatively little about the effect of amyloid on human nerve cells. 

What does this project involve?

Professor Salinas and her team want to learn more about the role of Wnts and synapses in Alzheimer’s disease using human nerve cells derived from induced-pluripotent stem cells (iPSCs). These cells are generated from skin cells which are reprogrammed to form nerve cells found in the brain.  

The research team will aim to understand more about the role of Wnts in the formation and maturation of synapses using these human nerve cells. They will look at the effects of adding Wnt proteins to the cells as they form to assess whether Wnts promotes the formation of synapses. Secondly they will investigate the impact of Wnts in protecting synapses against toxic amyloid.

 How will this project help people with dementia?

There has not been a new treatment for dementia in over 15 years and so researcher need to unearth the tiny changes in nerve cells that are causing the condition. This project will add to our understanding of the role of Wnt in the brain and help to find new targets for potential treatments.