Lab profile

The risk of Alzheimer’s disease (AD), the most common form of dementia, increases exponentially at ages over 65 years. Due to our ageing population demographic, the number of people with dementia in Australia is projected to grow (Alzheimer’s Australia). Research at all levels – cause, cure, prevention, delay and management, is required if we are to tackle this major health challenge and potential epidemic.

Our research aims to determine mechanisms of nerve cell dysfunction in AD with the overall goal of achieving a positive impact into understanding the underlying molecular cell biological causes of this and other neurodegenerative diseases.

In the AD brain, neuronal cytoskeletal rearrangement gives rise to rod-like inclusions containing hyperphosphorylated microtubule-associated protein (MAP) tau that form striations along neurites called neuropil threads. These structures often form near plaques of mis-folded amyloid-β (Aβ) peptides. The inclusions span the width of neurites, and there is evidence that they impair trafficking of vesicles and organelles to synaptic terminals. Whist little is known about their mechanism of assembly or how they impede neuronal function, these inclusions are a strong correlate to cognitive decline and a likely underlying molecular cause of AD. Our research addresses these important issues by focusing on the cause, mechanism and consequences of cytoskeletal rearrangement in neurons. Current work builds on our recent discovery that impairment of mitochondria, the cell’s energy producing structures, triggers the redistribution of tau to cytoskeletal rods and that their assembly invokes interactions of tau with elements of the actin cytoskeleton. The outcomes of our work may reveal new targets for interventions to prevent or reverse cytoskeletal rearrangements that have adverse effects on neuronal function.