DUAL AND MULTIPLE PROTEINOPATHIES IN NEURODEGENERATIVE DEMENTIAS – RISK FACTORS, PROGNOSTIC INDICATORS AND CLINICAL RAMIFICATIONS
Funder
National Health and Medical Research Council
Funding Amount
$604,644.00
Summary
Dementia is the umbrella term used to refer to a number of different clinical presentations,each associated with distinct histopathological signatures of protein aggregates and spread.However, converging evidence now suggests the common co-occurences of dual/multiple proteinopathies across dementia syndromes.The present study will identify the clinical ramifications and factors that are most predictive for such proteinopathies in a large cohort of longitudinally-studied patients with dementia.
Role Of Apolipoprotein D In Alzheimer's Disease And Frontotemporal Dementia
Funder
National Health and Medical Research Council
Funding Amount
$575,612.00
Summary
ApoD is a highly conserved lipocalin known for its antioxidant nature and role in regulation of inflammation. Oxidative stress and neuroinflammation are known to play a critical role in dementia. This project will study the association of apoD to inflammatory and oxidative stress markers in Alzheimer’s disease and Frontotemporal Dementia, two major forms of dementia. It will also examine the impact of apoD on disease pathology. Hence this project will lead us to therapeutic potentials of apoD.
Protecting Synaptic Connectivity In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$573,573.00
Summary
In Alzheimer’s disease, connections between neurons (synapses) are progressively damaged. The BACE inhibitor class of drugs entering Phase III clinical trials may slow the pace of neurodegeneration in patients with dementia. However, these drugs may simultaneously have negative effects on synapse function, learning and memory. This study will assess the effect of BACE inhibition on synapse properties and cognition and identify the contribution of key proteins affected by this treatment.
Combined TMS-EEG For Early Diagnosis Of Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$603,767.00
Summary
Early diagnosis of Alzheimer's disease is key to more effective early intervention. Current biomarkers are expensive and are not suited for detecting the subtle changes in brain function that occur during the initial stages of the disease. Non-invasive brain stimulation is pain-free and inexpensive, and can directly probe brain function in conscious humans. This project will investigate whether these techniques might be used to identify markers of early brain dysfunction in Alzheimer’s disease.
Pericyte Dysfunction Limiting Energy Supply In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$717,708.00
Summary
One possible cause of Alzheimer’s disease (AD) could be narrowing of small blood vessels (capillaries) within the brain, limiting blood flow and energy supply. Pericytes, a cell only on capillaries, maintain blood flow throughout the brain. I believe that pericytes may die in AD leading to an energy deficit and memory problems. I will test using human brains and animal models whether pericyte loss causes AD and how this is happening. Pericytes could provide a new therapy option for AD.
From Brain Maps To Mechanisms: Modelling The Pathophysiology Of Dementia
Funder
National Health and Medical Research Council
Funding Amount
$604,513.00
Summary
As the brain ages, the relationship between its structure and function also changes. In this study, I will use detailed computational modelling and extensive analyses of brain dynamics to improve interventional strategies by: 1. Characterising healthy and unhealthy brain dynamics during ageing; 2. Classifying the various subtypes of pathological dynamics; and 3. Predicting pathological neurodegeneration by identifying the earliest signs of perturbations in healthy ageing.
What Is The Effect Of Alzheimer’s Disease On Eye And Can Ocular Changes Be Used As Biomarker For Alzheimer’s Disease?
Funder
National Health and Medical Research Council
Funding Amount
$718,002.00
Summary
Visual symptoms are frequent early complaints in Alzheimer’s (AD) patients. Examining eyes can be a simple, specific and inexpensive way to assess and diagnose AD and fill in an urgent need for a viable biomarker. Retina is unique part of central nervous system that can be imaged non-invasively and thus serves as a ‘window to the brain”. Monitoring the eyes will also help prevent negative effects of AD on vision by way of timely intervention, in addition to providing mechanistic insights in AD.
Vascular Cognitive Risk Score: Quantifying The Vascular Burden In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$627,180.00
Summary
What causes dementia in a patient presenting to a clinic is often uncertain. While there are exciting potential treatments in the pipeline, we need to understand the cause of the disease in a specific patient to make correct treatment decisions. Stroke and other vascular diseases of the brain cause a significant proportion of dementia in the community. Using MRI scanning technology, this project will quantify this burden in a given patient by developing a ‘vascular cognitive risk' (VCR) score.
Treating Parkinson's Disease Dementia With Nanoscaffolds
Funder
National Health and Medical Research Council
Funding Amount
$665,144.00
Summary
Several diseases, including Parkinson’s disease (PD), result in dementia. Currently, pharmacological therapy is the only treatment for PD dementia, which only offers symptomatic relief with diminished efficacy. Therefore, there is a need to develop new strategies that prevent or slow the onset of dementia. This study will utilize nanoscaffolds that facilitate the controlled delivery of therapeutic proteins to prevent or slow the death of neurons associated with dementia in PD patients.
L1 Retrotransposition: The Missing Link Between Genetics And Environmental Factors In Parkinson's Disease ?
Funder
National Health and Medical Research Council
Funding Amount
$604,644.00
Summary
The study proposed here focuses on understanding the role of specific mobile DNA sequences in the interaction between environmental and genetic risk factors causing Parkinson’s disease (PD) leading to dementia. The project proposes identification of mobile DNA induced mutations in post-mortem human PD patient brain samples. The significance and mechanisms of mobile DNA induced mutations will be then tested in a PD mouse model.