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Non-Alzheimer Dementia: Pathogenesis And Clinicopathological Correlations
Funder
National Health and Medical Research Council
Funding Amount
$437,036.00
Summary
Dementia affects as many as 20% of people in their eighties. Although much of this is caused by Alzheimer's disease (AD), other types of dementia are also important. In this study we will look at two types of non-Alzheimer dementia, frontotemporal dementia (FTD) and small vessel cerebrovascular disease (SVD). The clinical symptoms of SVD closely resemble AD. Conversely, FTD results in degeneration of those parts of the brain which are responsible for personality, behaviour and language. We will ....Dementia affects as many as 20% of people in their eighties. Although much of this is caused by Alzheimer's disease (AD), other types of dementia are also important. In this study we will look at two types of non-Alzheimer dementia, frontotemporal dementia (FTD) and small vessel cerebrovascular disease (SVD). The clinical symptoms of SVD closely resemble AD. Conversely, FTD results in degeneration of those parts of the brain which are responsible for personality, behaviour and language. We will look at the brains of patients who have died with these diseases and determine the types of neurons which are damaged and their distribution in the brain. We will also investigate whether an individual's genetic make-up influences the development of SVD. In addition, in collaboration with neuropathologists across Australia, we will develop and standardise criteria for the pathological diagnosis of these diseases. Overall, this study will better characterise the pathology of two commonly encountered non-AD dementias and provide valuable insights into their causes.Read moreRead less
Effects Of Pharmacological Modification Of Ion Channel Activity On The Excitability Of Normal And Diabetic Nerves.
Funder
National Health and Medical Research Council
Funding Amount
$389,232.00
Summary
Neuropathic disturbances due to diabetes can destroy the quality of life and place a major cost burden on society. This project will provide insight into the actions of specific pharmaceutical agents on human nerves in both healthy subjects and diabetic patients with a view to establishing how these drugs reduce neuropathic symptoms in real life. The study will provide information regarding the underlying causes of neuropathic symptoms in diabetes and may help guide future treatments.
The Adverse Effects Of Diabetes On Stroke: An Echoplanar MRI Study
Funder
National Health and Medical Research Council
Funding Amount
$278,418.00
Summary
Stroke is the most common, major brain disease in Australia. It is the third most common cause of death and the most common cause of adult disability. There is a close link between diabetes and stroke. Firstly, diabetes is an important risk factor for the development of stroke. Secondly, about one third of stroke patients have diabetes. In general, their outcome is much worse than other patients. In fact little is known about the cause of this adverse effect in stroke patients and there is uncer ....Stroke is the most common, major brain disease in Australia. It is the third most common cause of death and the most common cause of adult disability. There is a close link between diabetes and stroke. Firstly, diabetes is an important risk factor for the development of stroke. Secondly, about one third of stroke patients have diabetes. In general, their outcome is much worse than other patients. In fact little is known about the cause of this adverse effect in stroke patients and there is uncertainty whether intensive control of blood sugar in acute stroke improves outcome. Our pilot work suggests that raised brain lactate, together with larger stroke size, might together be responsible for the worse outcome in diabetic patients. We can now measure brain lactate and stroke size with new MRI techniques called echoplanar MRI, which can allow measurements of brain chemistry, blood flow, potentially viable and dead tissue. A new monitoring device allows non-invasive measurement of blood sugar every 5 minutes. Using these strategies, we are planning a comprehensive study of the causes of the worse stroke outcome with diabetes. In addition, we are incorporating a study to determine whether intensive control of blood sugar in the first 3 days after stroke, compared with standard treatment, reduces brain lactate and growth of the actual stroke. An understanding of these effects will have important implications for the acute treatment of stroke patients. If we can show that rigorous control of blood sugar reduces brain lactate and stroke growth, our study will lay the ground work for a large clinical trial. This could have important implications, both in Australia, and overseas.Read moreRead less
Understanding The Variation In Frontotemporal Dementia
Funder
National Health and Medical Research Council
Funding Amount
$417,750.00
Summary
Frontotemporal dementia (FTD) is one of the non-Alzheimer dementias which accounts for between 12 and 20% of all dementia and as much as 50% of early onset dementia. It is characterised by marked behavioural change and thus patients with this disease present a major management challenge. The cause of FTD is unknown and at present there is no effective treatment for the disease. There are a number of different clinical subtypes of FTD, namely behavioural variant, language variant, and FTD with mo ....Frontotemporal dementia (FTD) is one of the non-Alzheimer dementias which accounts for between 12 and 20% of all dementia and as much as 50% of early onset dementia. It is characterised by marked behavioural change and thus patients with this disease present a major management challenge. The cause of FTD is unknown and at present there is no effective treatment for the disease. There are a number of different clinical subtypes of FTD, namely behavioural variant, language variant, and FTD with motor neuron disease (FTD+MND). Similarly there are pathological subtypes of FTD (Pick's disease, frontotemporal lobar degeneration and FTD with ubiquitin-positive MND inclusions). However, there appears to be little correspondence between these two subdivisions. The purpose of this study is to investigate the pathological differences and similarities between the different clinical subtypes of FTD. Furthermore, we will investigate the changes in brain atrophy which occur over the course of the disease to allow us to understand better the initial focus of the disease. We will also evaluate the role of cellular protein changes (ubiquitin and tau) in the pathogenesis of neuronal death. This research will allow us (i) to better diagnose and characterise FTD and (ii) establish any common mechanisms of neurodegeneration in the subtypes of FTD.Read moreRead less
Identifying Genes In The HLA Complex That Influence Clinical Course And Susceptibility In Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$725,177.00
Summary
There is no cure for multiple sclerosis (MS), but a person's genetic make-up can influence their susceptibility to developing MS and the symptoms of their condition. Knowing more about these MS genes will help to a) provide better advice concerning a person's risk of developing the disease or their prognosis b) in the design of new treatments. This project aims to identify 'MS genes in a region of the human genome call the HLA complex.
Amyloid Abeta In The Natural History Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$220,475.00
Summary
This grant is the continuation of a large series of experiments designed to uncover the basic causes of Alzheimer's disease. The focus is on closing some of the gaps in our knowledge of the natural history of Alzheimer's disease in relation to the deposition of the Abeta amyloid protein in the brain, which we believe plays a central role in the degeneration of nerve cells in this condition. The main questions we are tackling include: the feasibility of using assays of Abeta in the blood as a bio ....This grant is the continuation of a large series of experiments designed to uncover the basic causes of Alzheimer's disease. The focus is on closing some of the gaps in our knowledge of the natural history of Alzheimer's disease in relation to the deposition of the Abeta amyloid protein in the brain, which we believe plays a central role in the degeneration of nerve cells in this condition. The main questions we are tackling include: the feasibility of using assays of Abeta in the blood as a biological marker of Alzheimer's disease; whether better transgenic mouse models of Alzheimer's disease are required; whether the soluble forms of Abeta amyloid are the major species which cause neurotoxicity (in contrast to the insoluble forms which constitute the bulk of this protein in the Alzheimer's disease brain); and whether the intracellular or extracellular pathways of Abeta aggregation and toxicity are the key to understanding this disease. Increasing evidence suggests that the clearance of soluble forms of the Abeta protein from the brain may be a major therapeutic strategy. We therefore require further investigations of how these soluble forms of Abeta are generated in nerve cells, and how these forms exist in equilibrium with soluble and insoluble pools in the brain, cerebrospinal fluid, blood and other tissues of the body.Read moreRead less
The Role Of Notch Signalling In Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy, caused by a lack of a protein called dystrophin. Dystrophic muscles are fragile, prone to injury, and have a compromised ability to regenerate after damage. Defective Notch signalling has been implicated in the poor regenerative response of aged muscles and similarly in dystrophy based on our preliminary data. Modulating Notch signalling could therefore delay the onset or slow the progression of DMD.
Australian Stroke Genetics Collaborative - Genome-wide Association Study In Ischaemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$1,141,037.00
Summary
The majority of stroke is caused by atherothrombosis, the formation of blood clots in brain blood vessels. Numerous genes are linked to atherothrombosis, but many studies examined genetic influences in isolation from environmental risk factors. We will examine the relevance of genetic variations linked to atherothrombosis, in the context of environmental risk factors. By determining the contribution of genetic and environmental factors in stroke, we will develop a stroke risk assessment tool.