A key feature of the diseases that cause dementia are proteins that stop doing their normal job, take on toxic properties and clump together. Understanding the processes underlying these changes could reveal potential new ways to tackle dementia. This project sets out to gain important clues about tau protein, which forms clumps in both Alzheimer’s and frontotemporal dementia. Certain parts of nerve cells appear to be more susceptible to being sites of tau build ups, so the team will scrutinize different parts of nerve cells to discover whether there are fundamental molecular differences that could underlie this.
Tau protein is one of the key culprits in Alzheimer’s disease and frontotemporal dementia, found in clumps within nerve cells and causing cells to die. However, these clumps are thought to be a late stage, and in recent years much effort has gone into revealing the first steps that tau takes along the road to wreaking havoc in the brain.
Dr Katrin Deinhardt and her team have been studying tau, tracking how the toxic form spreads from one nerve cell to the next. They recently made an intriguing observation that when toxic tau first enters a new nerve cell, it does not start to build up near the site of entry but at the other end of the nerve cell. If the team can reveal why certain regions in nerve cells are more sensitive to the detrimental effects of tau, they may uncover key protective factors within nerve cells that could be boosted to try and stop the build-up of tau anywhere in nerve cells.
Using specialised chambers, Dr Deinhardt’s team are already able to follow how tau spreads from one nerve cell to another. Now they will adapt these chambers to study individual nerve cells to look at the tau located within it and decipher the molecular differences between different areas of the nerve cell. They will take a preliminary look at proteins and processes associated with the internal scaffolding of nerve cells, as well as helper proteins that check other proteins for correct folding and that they are working properly. If they find key regional differences in nerve cells, they can then explore this further in future work which could reveal potential processes to target with new treatments.
Dr Katrin Deinhardt
University of Southampton
1 October 2017 - 30 September 2018
Full project name
Dissecting the molecular basis of selective axonal subcompartment vulnerability in tauopathy