Stichting Alzheimer Onderzoek
Unravelling cell-type specific vulnerability pathways in response to pathogenic tau and a-synuclein
Support
€ 100,000In this project we want to find new factors that can prevent brain cell loss in certain dementias. This is important, because this loss is what causes many symptoms and we currently have no drugs that can efficiently stop this. We know that in many neurodegenerative diseases certain proteins aberrantly precipitate within individual brain cells, which then causes damage. Yet while some brain cells seem to be highly vulnerable to these changes, others are not. We want to unravel the secrets of these protected cells, as this might give us the body’s very own road-map as to how we can treat vulnerable cells – e.g. those cells that when lost cause memory impairment in Alzheimer’s disease. We make use of a powerful model – the fruit fly, which we have genetically modified to express these precipitating proteins. Because their brains are much smaller than human brains, we can now assess their entire brains with all their >200 unique cell types at the same time. With modern microfluidics technology this allows us to ‘read’ the inner workings of >10 000 individual cells at the same time, which is how we then extract the differences between ‘weak’ and ‘strong’ cells.
The best outcome of this research in our fruit fly models would be to find new factors protecting against neuronal loss triggered by aberrant protein precipitation. Upon successful completion we will publish these findings, which will then allow other scientists to build on these results. Beyond this 2-year grant also we ourselves plan to assess the most promising hits in human disease model brain cells that are derived from stem cells.