Alzheimer’s disease (AD), is the most common form of dementia, accounting for between 50-70% of all cases. There is general agreement that current treatments for AD/dementia are inadequate so new treatment strategies are desperately needed. I am addressing these challenges by developing new technologies to generate next generation treatments for AD.
Implications Of Retinal Neurodegeneration In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$602,213.00
Summary
Recent research has shown that “early signs” of Alzheimer ’s disease (AD) can be detected in the eyes. My research focus is to determine which particular changes in the retina are associated with AD. I will also investigate if blocking the production of beta amyloids (proteins produced in AD) in the eye will indeed help reduce their load in the brain and hence delay the onset of AD. Results from this research maybe used for early diagnosis and future medicinal studies that target the eye in AD.
Dementia is the third leading cause of death in Australia and the single greatest cause of disability in the elderly. Current therapies for Alzheimer’s disease (AD), the most common form of dementia, are inadequate and fundamentally new treatment approaches are required. The aim of this proposal is to develop novel drug candidates for the treatment and prevention of AD and other neurodegenerative disorders by targeting a class of cell-surface receptors called G protein-coupled receptors (GPCRs).
Neuroprotective Functions Of Autophagy Regulators In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
The accumulation of the beta amyloid protein has a central role in AD and enhancing its removal improves memory loss in animal AD models. This project builds on my recent finding of regulators of a cell housekeeping system, “autophagy” which accelerate removal of beta amyloid in cells. This study will advance knowledge into the protective functions of the autophagy regulators in reducing AD symptoms. Findings from this work might provide the basis for developing effective anti-AD therapeutics.
The Role Of Copper In Ubiquitin-dependent Protein Degradation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$588,622.00
Summary
Ubiquitin’s are small proteins that tag other proteins in a process known as “Ubiquitination”. Often this is to target them for degradation once they are no longer needed i.e. to take out the rubbish. This process is disrupted in Alzheimer’s disease (AD), which may contribute to the disease. This project aims to find out if copper, an essential metal for life, is required for this process. Drugs that are designed to deliver copper to brain cells have been effective in small AD clinical trials.
Optimising Exercise Prescription For Brain Health In Older Adults At Risk Of Dementia
Funder
National Health and Medical Research Council
Funding Amount
$594,123.00
Summary
To reduce dementia burdens in the community, cost effective and targeted early regenerative strategies are critical. Engaging in frequent aerobic exercise is one strategy that can delay the onset and slow the progression of dementia. However, prescription is limited by an incomplete understanding of how exercise positively influences brain health. Here I will investigate the influence of current exercise levels, intensity and exercise environment on brain health in adults at risk of dementia.
Investigating The Iron Proteome In Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$514,644.00
Summary
Iron is essential for brain function. When the delicate balance of metals in the brain is disturbed, neurodegenerative effects such as those seen in Alzheimer’s disease are observed. Although we know there is a link between iron and Alzheimer’s disease, we do not know which specific iron proteins are involved. This project will provide the first characterisation of different iron proteins in the brain to understand the mechanisms of disease and help in the search for new treatments.
How Do Mutations In Autophagy Receptors Cause FTD And ALS?
Funder
National Health and Medical Research Council
Funding Amount
$566,966.00
Summary
As cells age the "garbage disposal" process within cells slows down, becoming less functional. In inherited forms of dementia the genes involved often code for damaged proteins that "clog up" the disposal system or directly affect the “garbage men”. These defective garbage men genes include SQSTM1/p62, OPTN, VCP and UBQLN2. We will determine how these defective genes lead to build up of garbage in neuronal cells and how leads to disease.
Stand Up To Dementia: Reducing Prolonged Sitting To Improve Cognitive Function In Older Adults
Funder
National Health and Medical Research Council
Funding Amount
$603,901.00
Summary
Australia has an ageing population, resulting in more people being diagnosed with dementia. Prolonged sitting - (a behaviour that is very common amongst older adults) may increase the risk of cognitive decline and thus developing dementia. This study aims to further explore the relationship of sitting with dementia and cognitive function by using objective measures of sitting and also to develop programs and resources to reduce prolonged sitting which are informed by consumers.
Development Of Blood-based Biomarkers For The Early Detection Of Brain Amyloid And The Investigation Of The Natural History Of Alzheimer’s Disease.
Funder
National Health and Medical Research Council
Funding Amount
$720,144.00
Summary
To have a direct impact on the diagnosis and treatment of Alzheimer’s and other neurodegenerative diseases we need a detailed molecular understanding of the proteins that drive the disease. My laboratory develops and applies the most advanced analytical tools available to develop blood-based markers that can detect the development of Alzheimer’s disease before symptoms occur. This Fellowship will allow me to expand our understanding of the natural history of Alzheimer’s disease.