Inclusion Body Proteins And Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$389,164.00
Summary
Parkinson's disease affects 1% of people aged over 50, and a related disorder, Dementia with Lewy bodies, causes dementia in elderly patients. These diseases are characterised by inclusion bodies (Lewy bodies) in a sub population of nerve cells. Multiple system atrophy, another adult-onset neurodegenerative disorder, is also characterised by inclusion bodies (glial inclusions). Inclusions may interfere with cellular function, contributing to the process of brain degeneration. The inclusion bodie ....Parkinson's disease affects 1% of people aged over 50, and a related disorder, Dementia with Lewy bodies, causes dementia in elderly patients. These diseases are characterised by inclusion bodies (Lewy bodies) in a sub population of nerve cells. Multiple system atrophy, another adult-onset neurodegenerative disorder, is also characterised by inclusion bodies (glial inclusions). Inclusions may interfere with cellular function, contributing to the process of brain degeneration. The inclusion bodies are precipitations of proteins and other cellular chemicals. In the last 10 years, in a search for the underlying cause of these neurodegenerative disorders, there has been an intensive research effort to identify the proteins precipitated in the inclusion bodies. The present project adopts a new strategy and aims to identify the precipitated proteins in the inclusion bodies in brains of people dying with Parkinson's disease, Dementia with Lewy bodies and Multiple system atrophy. We intend to isolate the Lewy bodies and the glial inclusions from fresh brain tissue of patients dying with relevant diseases. Throughout the various steps in the isolation process, the location of the inclusion bodies will be checked with a special antibody to a particular protein (alpha synuclein) which we and others have already discovered to be present in all inclusion bodies. Proteins will then be identified using electrophoresis and amino acid sequencing. With the identification of these proteins, their role in neurodegeneration in these diseases can be examined using multiple biomedical approaches. These proteins will be important candidates for developing novel diagnostic reagents, screening for gene mutations in patients, or as the target of therapeutic intervention in these diseases.Read moreRead less
Blood Proteins For Early Discrimination Of DEmentias
Funder
National Health and Medical Research Council
Funding Amount
$498,412.00
Summary
bPRIDE aims to develop blood biomarkers for early and specific diagnosis of the main dementia types: Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, and use these to develop diagnostic tests.
Investigating Biometal Dyshomeostasis In Dementia With Lewy Bodies
Funder
National Health and Medical Research Council
Funding Amount
$554,644.00
Summary
Dementia with Lewy bodies (DLB) is the second most common form of dementia after Alzheimer's disease (AD). Very little is known about what causes DLB and there are currently no effective therapeutics. An imbalance in naturally occurring biological metals such as iron and copper have been implicated in AD and Parkinson’s disease so this project will investigate if metals are involved in DLB. The ultimate goal of this project is to identify if metals are a valid target for future drug development.
Lewy Bodies In Patients With Dementia – Determining Common And Unique Mechanisms In Relation To Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$604,644.00
Summary
Alzheimer’s disease is the most common type of dementia but often has multiple mixed pathologies. For example, Alzheimer post mortem brains may have abnormal accumulation of Lewy bodies in certain parts of the brains, and could be diagnosed as Lewy body disease. This may represent a skewed representation of some dementia subtypes. This project will identify the biological determinants of dementia patients with Lewy body disease for better understanding and future therapeutic targeting.
Non-Alzheimer’s Disease Degenerative Dementias: Identifying Prodromal Genetic/familial Phenotypes, Modifying Factors, And Protein Variations Involved In Progression
Funder
National Health and Medical Research Council
Funding Amount
$6,449,246.00
Summary
This proposal will generate new knowledge necessary for advancing the diagnosis of the non-Alzheimer’s disease dementias. We will identify the preclinical forms of frontotemporal dementia and Lewy body dementia using similar methods to those successfully employed to advance diagnosis of Alzheimer’s disease. Importantly, our team has the capacity to translate these protocols into clinical practice and into further advances in biological knowledge that is necessary for future therapeutic targeting
Identifying Neuroimaging Based Biomarkers For Predicting Clinical Progression Along The Lewy Body Disease Spectrum
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Lewy body dementias (LBD) comprise similar but heterogenous group of poorly understood disabling neurodegenerative conditions. This project aims to apply advanced neuroimaging techniques and novel psychological testing to patients at risk of Lewy body disorders as well individuals with established disease to identify novel biomarkers that may explain symptoms of these disorders as well as help predict development of LBD at its early stages when it may be amenable to neuroprotective treatments.
Dementia Related Deficits In Striatal Cholinergic Function And Decision-making
Funder
National Health and Medical Research Council
Funding Amount
$414,370.00
Summary
This proposal will provide essential new information on the role of deficits in decision-making associated with Parkinson’s disease dementia. We will use an innovative animal model to assess the influence of neurodegeneration and neuroinflammation the consequent loss of function in the neuronal systems supporting the learning and memory processes that contribute to goal-directed action, particularly the way new learning interacts with existing memory to guide choice and decision-making.
Feasibility Of Minimally Invasive Deep Brain Stimulation Via An Endovascular Stent-electrode.
Funder
National Health and Medical Research Council
Funding Amount
$122,032.00
Summary
Neurocognitive decline in Parkinson's disease refers to the non-motor symptoms of the disease; these symptoms have increasingly become recognised as both prevalent, and evolving early in the disease course. While motor symptoms are treated with drugs and electrodes, the changes to patients� cognition, the progressive dementia, the psychosis and other symptoms progress with poor treatment. This research is designed to identify and understand targets so better treatments can be created.