Research highlights and societal impact

The risk of Alzheimer’s disease (AD), the most common form of dementia, increases exponentially at ages >65 years. Due to our rapidly ageing population, between 2000 and 2050, the number of people with dementia in Australia is expected to increase by 327%, while the total population increases by less than 40% (Alzheimer’s Australia). The total financial cost of dementia in 2002 was $6.6 billion; by 2051 the impact will increase threefold to a total of 3.3% of GDP (Access Economics). Research at all levels – cause, cure, prevention, delay and management are required if we are to tackle this major health challenge and impending 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 disease.

In the AD brain, rod-like cytoskeletal inclusions containing hyperphosphorylated tau protein (tau rods) form striations in neurites called “neuropil threads” (Panel 1). These structures often form near plaques of mis-folded amyloid-β (Aβ) peptides, are a strong correlate to cognitive decline and a likely underlying molecular cause of the disease. The rods span the width of neurites and there is evidence that they impair trafficking of vesicles and organelles to synaptic terminals. However little is known about their mechanism of assembly or how they impede neuronal function. Our research addresses this important issue, by focusing on the cause, mechanism and consequences of tau rod assembly in neurons. Current work builds on our new discovery that impairment of mitochondria, the cell’s energy producing structures, causes the formation of tau rods (Panels 2,3) and that their assembly invokes novel interactions of tau with elements of the actin cytoskeleton1. The outcomes of our work will reveal new targets for vital future interventions to prevent the assembly of tau rods and their adverse effects on neuronal function.