Completing the tauopathy puzzle - modelling novel mutations to uncover unknown roles for tau in neurodevelopment and neurodegeneration
A chromosomal band called 17q21.31 is a ‘genetic postcode’ and the most famous gene that resides at this address is MAPT (microtubule-associated protein tau). The MAPT gene is significant in dementia research, as variations in it are linked to several types of dementia. MAPT encodes a protein called tau, which is important for healthy brain function. However, in some forms of dementia, something goes wrong, causing tau to become pathological. The 17q21.31 genetic postcode is a hotspot for these types of changes. Recently, new genetic changes in 17q21.31 were identified in patients with unexplained dementia-like symptoms, who also had pathological tau deposits in their brains. Most of these patients were children and adolescents, so it is possible they could be classified as having childhood dementia. Unfortunately, scientists don’t know why this genetic change occurs, or which parts of the brain are involved. Dr Bright will study human stem cells and brain organoids, also known as “mini brains”, in a petri dish. This will allow her to model the hallmark brain changes that occur because of these genetic changes. This project will provide significant understanding of dementias that exhibit abnormal tau deposits within the brain and further explore the role of tau in the brain across ageing. The results of this project will enable the discovery and development of tailored, disease-specific drug treatments for tau-related dementias.
Dr Fiona Bright is a postdoctoral research fellow at the Dementia Research Centre within Macquarie University Medical School. She has a background in paediatric neuropathology and expertise in early-onset neurodegenerative diseases, including frontotemporal dementia.