Apolipoprotein A-I-stimulated Secretion Of Apolipoprotein E By Human Foam Cell Macrophages.
Funder
National Health and Medical Research Council
Funding Amount
$201,208.00
Summary
Atherosclerosis is the disease which causes narrowings in arteries underlying such serious conditions as heart attack and stroke. A key component of the formation of atherosclerotic narrowings in arteries is the accumulation of fat-filled cells called foam cell macrophages. These foam cells can be stimulated to secrete a special molecule called apolipoprotein E (or apo E), which reduces the amount of atherosclerosis. We have found that we can stimulate foam cells to secrete this protein by addin ....Atherosclerosis is the disease which causes narrowings in arteries underlying such serious conditions as heart attack and stroke. A key component of the formation of atherosclerotic narrowings in arteries is the accumulation of fat-filled cells called foam cell macrophages. These foam cells can be stimulated to secrete a special molecule called apolipoprotein E (or apo E), which reduces the amount of atherosclerosis. We have found that we can stimulate foam cells to secrete this protein by adding to them another molecule called apo A-I. This project will investigate how apo A-I stimulates the foam cells to secrete apo E. In this way we will be able to regulate the secretion of apo E, and be able to increase its secretion. This may result in our being able to treat or prevent atherosclerosis.Read moreRead less
Novel Mechanisms And Diagnostic Applications For Iron In Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$599,644.00
Summary
My recent findings showed that measuring the iron content of the brain, by looking at the fluid surrounding the brain, was useful in predicting the chances of developing Alzheimer’s disease, and predicting the severity of this disease. Here, I will investigate this in more depth, and in new patient groups. The project has the potential to characterise a new way of predicting Alzheimer’s disease, and also will help inform how Alzheimer’s disease develops.
Genetic Mechanisms That Moderate Effects Of Aβ Accumulation In Preclinical Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$603,525.00
Summary
Alzheimer’s disease (AD) is the most common form of dementia, and the number of people living with it will triple by 2050. There is currently no cure for AD, and the only means of slow the growing epidemic is to delay onset. We propose to understand the complex interplay between genetic, cognitive, neuroimaging and biological markers of AD in order to better understand the disease process, and in turn identify high-risk individuals for clinical trials and uncover disease-modifying strategies.
The Impact Of The Environment And Pollution On Cognitive Health (EPOCH): Building The Knowledge Base Through International Collaboration
Funder
National Health and Medical Research Council
Funding Amount
$681,240.00
Summary
Neighbourhood environments can impact on the health of their residents. However, not much is known about their effects on cognitive decline in late life. This project will link environmental data to existing studies on ageing to examine how the neighbourhood built environment (e.g., access to services), natural environment, air pollution and noise may impact on cognitive decline and the risk of dementia in older adults and whether these effects differ in the United Kingdom and Australia.
Targeting Inflammation As A Biomarker And Treatment For Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$718,920.00
Summary
We are undertaking the challenge of using and developing novel animal models in parallel with studies on affected human subjects to elucidate the underlying molecular mechanisms linking the changes in inflammation to amyloid plaques, neurofibrillary tangles and cognitive decline. Understanding these mechanisms will allow us to define the biological pathways involved in the onset and progression of Alzheimer’s disease, and identify potential biomarkers and therapeutic targets.
The Interactive Effects Of Dietary Saturated Fat And Apolipoprotein-E Genotype On Peripheral Metabolism Of Lipoprotein-amyloid And Neurovascular Integrity.
Funder
National Health and Medical Research Council
Funding Amount
$637,536.00
Summary
This project is based on a remarkable discovery which suggests that in some individuals, Alzheimer's disease may be a consequence of corruption of microscopic blood vessels that supply brain, damaged as a consequence of exaggerated exposure in blood to a protein produced principally in liver. The project will explore this pathway further in subjects at heightened risk of Alzheimer's disease and in humanised animal models. The findings may provide new opportunities for prevention and treatment.
Myelin Lipid Breakdown Affected By Apolipoprotein E Genotype: Implications For Alzheimer’s Disease Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$534,644.00
Summary
This project pieces together two important questions about Alzheimer’s Disease: (1) Why a naturally occurring variant of a gene called “APOE“ is the primary genetic risk for Alzheimer’s. (2) Why Alzheimer’s preferentially affects brain regions that lose a fatty substance called myelin, the electrical insulation of the brain. In doing so, we will understand more about what makes people more susceptible to Alzheimer’s and whether therapies to restore myelin could be effective against Alzheimer’s.
Therapeutically Targeting The Major Genetic Risk Factor Of Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$530,069.00
Summary
The second greatest risk factor for Alzheimer’s disease (after age) is genetic variation in a protein called APOE, however it is unknown why APOE increases the risk of disease. We have new clinical and laboratory evidence that APOE incresase risk of Alzheimer’s disease by manipulating iron pathways in the brain. We plan to examine these pathways and apply a new theraputic we have developed that targets these pathways in animal models of Alzheimer’s disease.