Fiona Bright

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. 

Through this grant, Dr Fiona Bright has created childhood dementia “mini-brains” using human stem cells and brain organoids. These act like 3D models in a petri dish that allow the replication of the hallmark brain changes that occur because of genetic changes such as in 17q21.31. Using these “mini-brains”, Dr Bright has identified a trend in accelerated ageing in childhood dementia. This indicates that brain ageing may occur much faster in childhood dementia, accelerating cognitive decline. Dr Bright has also found some drugs, including anti-ageing drugs, were able to rescue brain cells from damage and prevent harmful inflammation in her “mini-brains”. Her findings provide critical insights into brain ageing. Moving forward, Dr Bright aims to investigate these findings further, trying to get to the bottom of how and why these changes may occur.

This project has added significantly to the understanding of dementias that exhibit abnormal tau deposits within the brain. The results of this project will enable the discovery and development of tailored, disease-specific drug treatments for tau-related dementias.

Read more about this exciting project

At the time of this award, Dr Fiona Bright was a postdoctoral research fellow at the Dementia Research Centre within Macquarie University Medical School. Her background is in paediatric neuropathology and she has expertise in early-onset neurodegenerative diseases, including frontotemporal dementia.