The Role Of Gonadotropins In Regulating The Production Of Alzheimer's Beta Amyloid
Funder
National Health and Medical Research Council
Funding Amount
$400,278.00
Summary
Currently, about 160,000 Australians suffer from dementia; of which 50-70% are Alzheimer's disease (AD) cases. AD is characterised clinically by memory and personality changes and pathologically by deposition of amyloid. Of particular importance in the disease pathogenesis, is a small molecule called beta amyloid, of which the overproduction is thought to be central to the development of AD. Changes in the levels of the reproductive hormones, particularly low levels of oestrogen during menopause ....Currently, about 160,000 Australians suffer from dementia; of which 50-70% are Alzheimer's disease (AD) cases. AD is characterised clinically by memory and personality changes and pathologically by deposition of amyloid. Of particular importance in the disease pathogenesis, is a small molecule called beta amyloid, of which the overproduction is thought to be central to the development of AD. Changes in the levels of the reproductive hormones, particularly low levels of oestrogen during menopause or testosterone during andropuase, has been associated with the increased risk of developing AD and in altering the levels of beta amyloid. Furthermore, menopause and andropause are also characterised by changes in other reproductive hormones such as the gonadotropins. High levels of the gonadotropins have also been associated with the increased risk of developing AD. Therefore it is important to identify how these changes modify the risk of developing AD. This study examines the role of the gonadotropins in regulating beta amyloid levels in cell culture and in an animal model for AD. Furthermore, this study will assess, in the animal model, the use of gonadotropin lowering agents to reduce levels of beta amyloid. The results from this study will provide important data on how reproductive hormones regulate beta amyloid. Further insight into these mechanisms will provide therapeutic or preventative strategies for AD.Read moreRead less
The research outlined in this application seeks to examine the role of calcium in the pathogenesis of AD. It will examine the hypothesis that the build-up of a protein known as the Abeta causes an increase in levels of calcium in nerve cells of the brain. This increase in calcium may trigger nerve cell damage and dementia. The ultimate aim of the research is to identify new targets for drug development in Alzheimer's disease.
A Role Of Sortilin In The Development Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Summary
Alzheimer’s disease is the most common form of dementia and is caused by both environmental and genetic variations. With aging, a toxic peptide accumulates in the brain and causes loss of memory and cell death. This study aims to elucidate how the toxic peptide is generated and how its precursor trafficks within nerve cells.
The Role Of A Presenilin 2 Truncation (PS2V) In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$552,741.00
Summary
The Presenilin and APP proteins are centrally important in inherited, early onset Alzheimer's disease. We have discovered that a shortened form of Presenilin protein, "PS2V", appears to increase specifically the rate at which the APP protein is cleaved to produce the "Amyloid beta" protein fragment that is found in Alzheimer's disease brains. This occurs when brain cells are under oxidative stress. Understanding this process will facilitate development of appropriate therapeutic strategies for t ....The Presenilin and APP proteins are centrally important in inherited, early onset Alzheimer's disease. We have discovered that a shortened form of Presenilin protein, "PS2V", appears to increase specifically the rate at which the APP protein is cleaved to produce the "Amyloid beta" protein fragment that is found in Alzheimer's disease brains. This occurs when brain cells are under oxidative stress. Understanding this process will facilitate development of appropriate therapeutic strategies for the disease.Read moreRead less
Sortilin Forms A Complex With APP And BACE To Regulate Abeta Production
Funder
National Health and Medical Research Council
Funding Amount
$208,910.00
Summary
Alzheimer's disease is a neurodegenerative disorder which is highly prevalent in aging population. Amyloid beta is a toxic peptide derived from a metabolic processing of its precursor amyloid precursor protein (APP). This project will examine how a novel protein called sortilin interacts with APP and its processing enzyme and how the toxic peptide is produced. Understanding the trafficking of APP and beta-secretase ?BACE? regulated by sortilin may help understanding how Alzheimer's disease is de ....Alzheimer's disease is a neurodegenerative disorder which is highly prevalent in aging population. Amyloid beta is a toxic peptide derived from a metabolic processing of its precursor amyloid precursor protein (APP). This project will examine how a novel protein called sortilin interacts with APP and its processing enzyme and how the toxic peptide is produced. Understanding the trafficking of APP and beta-secretase ?BACE? regulated by sortilin may help understanding how Alzheimer's disease is developed.Read moreRead less
Use Of The P75NTR Extracellular Domain As A Therapeutic Target For The Treatment Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$733,633.00
Summary
AlzheimerÍs disease is the most common form of dementia and is caused by both environmental and genetic variations. With aging, a toxic peptide accumulates in the brain and causes loss of memory and cell death. This study aims to elucidate how the toxic peptide is generated and how to remove it in order to prevent and treat the disease.
I am a molecular and cellular biologist determining the molecular mechanisms responsible for the neurodegeneration in Alzheimer’s, Parkinson’s and Prion disease.
Delineating The Mechanism Of Amyloid Beta Toxicity
Funder
National Health and Medical Research Council
Funding Amount
$565,242.00
Summary
Alzheimer’s disease and beta amyloid toxicity: Alzheimer’s disease (AD) is the most common form of dementia and is characterized by progressive memory loss, confusion, and cognitive deficits. In 2011, an estimated 269,000 Australians are currently living with dementia and without a significant medical breakthrough soon, it is anticipated that this will rise to about 981,000 by 2050
Enhancing Peripheral Clearance Of Beta Amyloid As A Treatment For Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$548,681.00
Summary
Amyloid-beta (abeta) accumulation in the brain is a key step in the development of Alzheimer's disease, with potential therapies focusing on its clearance. Compounds that bind abeta in blood have been shown to alter brain abeta levels. We will assess the efficacy of a novel abeta-binding peptide to promote peripheral clearance of brain-derived abeta in a mouse model of AD. Such a drug would be effective in sporadic AD, where the efflux transport, clearance and degradation systems are defective.
Molecular & Neuropsychological Predictive Markers Of Cognitive Decline.
Funder
National Health and Medical Research Council
Funding Amount
$429,500.00
Summary
Alzheimer's disease (AD) is a major cause of dementia in the elderly. As populations worldwide are living longer the prevalence of AD is predicted to rise markedly and in addition to the huge emotional burden on families the economic implications to the community at large is severe. Thus our aging veteran population and their spouses are particularly vulnerable to this devastating disease. Recent developments in AD research have resulted in a number of therapeutic strategies being undertaken wit ....Alzheimer's disease (AD) is a major cause of dementia in the elderly. As populations worldwide are living longer the prevalence of AD is predicted to rise markedly and in addition to the huge emotional burden on families the economic implications to the community at large is severe. Thus our aging veteran population and their spouses are particularly vulnerable to this devastating disease. Recent developments in AD research have resulted in a number of therapeutic strategies being undertaken with several of these now in phase 2 clinical trials. However for these treatments to be most effective early diagnosis is crucial. Currently, definite diagnosis is restricted to post-mortem examination of the brain for the presence of characteristic neuropathological features. This project proposes to identify individuals at high risk of developing cognitive decline leading to AD by using a battery of biochemical, genetic and neuropsychological markers. This study builds on our earlier work which followed a cohort of memory complainers and demonstrated that subjects in this group have lower cognitive scores and an increased frequency of the genetic risk factor, the e4 allele of apolipoprotein E. Follow up of this well studied cohort with more sensitive and extensive neuropsychological tests together with other genetic and biochemical markers will be important in identifying those risk factors that have positive predictive value for cognitive decline thereby contributing towards enhancing the therapeutic efficacy of current symptomatic and future drugs directed at the cause of AD.Read moreRead less