The Modulation Of Metals To Improve The Cognitive And Pathological Features Of Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$436,238.00
Summary
This proposal will characterise the effects of a novel therapy for the treatment of Alzheimer's disease. Our preliminary data show that this approach can affect both the onset and progression of the disease, as well as the symptoms that characterise it. Thus, a thorough assessment of these effects and this drug target provides a tangible movement towards a truly effective treatment for Alzheimer's disease.
The presenilin proteins are key components in the development of Alzheimer's disease. Mutations in these proteins can cause early Alzheimer's disease. We will continue our study of the biochemistry and cell biology of these proteins using tools and experimental models that we have already developed. This will provide important information on the mechanism of the disease process and give new leads in the treatment of the disease. The new technologies of genetic screening for presenilin mutations ....The presenilin proteins are key components in the development of Alzheimer's disease. Mutations in these proteins can cause early Alzheimer's disease. We will continue our study of the biochemistry and cell biology of these proteins using tools and experimental models that we have already developed. This will provide important information on the mechanism of the disease process and give new leads in the treatment of the disease. The new technologies of genetic screening for presenilin mutations will be developed and utilized as a National referral base.Read moreRead less
Delineating The Interaction Between The Amyloid Precursor Protein Family And SorLA-LR11
Funder
National Health and Medical Research Council
Funding Amount
$749,022.00
Summary
The Alzheimer's disease Amyloid Precursor Protein (APP) is central to the cause of Alzheimer's disease (AD). It's metabolised into the neurotoxic amyloid beta (Abeta) peptide that is deposited in AD brains. The sorLA protein is a neuronal protein that interacts with APP and alters its metabolism into Abeta. This grant will study the interaction between APP and sorLA and define the APP binding site for sorLA which represents a potential drug target.
Early Intervention For Amnestic Mild Cognitive Impairment : A Randomised Trial Of Memory Management
Funder
National Health and Medical Research Council
Funding Amount
$577,556.00
Summary
It is increasingly recognised that Alzheimer’s disease can emerge slowly over years and persons presenting with memory impairment, or mild cognitive impairment (MCI), are at increased risk of developing Alzheimer’s disease. Following diagnosis of MCI, active management through symptomatic drug treatment remains equivocal, therefore, memory impairment continues to be troublesome and patients and families are seeking interventions that offer improvement in quality of life. Cognitive interventions ....It is increasingly recognised that Alzheimer’s disease can emerge slowly over years and persons presenting with memory impairment, or mild cognitive impairment (MCI), are at increased risk of developing Alzheimer’s disease. Following diagnosis of MCI, active management through symptomatic drug treatment remains equivocal, therefore, memory impairment continues to be troublesome and patients and families are seeking interventions that offer improvement in quality of life. Cognitive interventions are low cost and, where effective, can provide a stand-alone intervention or add value to the pharmacological approach. The primary aim of this study is to evaluate whether an early intervention program of memory training is effective in improving use of memory strategies in everyday life, and whether this has psychological and emotional benefits for individuals with MCI and their families. We will evaluate through a randomised controlled trial the efficacy of a memory-group program which will involve the family and patient, rather than just the person with MCI, in developing increased awareness of memory issues and specific strategies to prevent memory failures. Over successive cohorts recruited from memory clinics, families will be randomly assigned to either an immediate intervention or a delayed intervention (waiting-list control) group. We will also recruit a sample of healthy older adults who will be similarly randomised into early and late intervention groups. Healthy older adults will provide a means of establishing whether any improvements in the MCI groups are (i) to the same extent as healthy older adults and (ii) to normative levels. Evaluation will be at pre- and post-intervention and at six months follow-up on tests of memory, questionnaires of knowledge and use of memory strategies in everyday life, and appraisal of level of wellbeing. Information about memory and systematic training in compensatory memory skills are expected to significantly improve the capacity of patients and families to cope with everyday memory difficulties. Through active participation in the management of memory impairment, it is expected that the level of wellbeing will increase, for both patient and families.Read moreRead less
Investigating The Role Of Exosomal Shuttle RNA In Mediating Pathogenesis Of Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
The risk for dementia increases with age and is placing a growing burden upon Australian medical resources. Novel genetic signals can be communicated between cells. This process may contribute to the development of dementia related disorders, such as Alzheimer's and Prion diseases. We hope to identify the genetic signals communicated between cells that may contribute to dementia. This will help us develop novel treatments that delay the onset or ultimately prevent Alzheimer's and Prion disease.
The Neural Reaction To Injury: Clues To The Cause And Prevention Of Acquired Brain Damage And Alzheimer's Disease.
Funder
National Health and Medical Research Council
Funding Amount
$390,326.00
Summary
The cellular mechanism underlying neuronal degeneration following head trauma and Alzheimer?s disease is not known and represents the major impediment to developing therapeutic strategies to protect nerve cells. This grant application will utilise a variety of modern research methods to determine the key changes in the brain that are associated with the response of nerve cells to physical trauma. These include not only the structural alterations that immediately follow such injury, but the compl ....The cellular mechanism underlying neuronal degeneration following head trauma and Alzheimer?s disease is not known and represents the major impediment to developing therapeutic strategies to protect nerve cells. This grant application will utilise a variety of modern research methods to determine the key changes in the brain that are associated with the response of nerve cells to physical trauma. These include not only the structural alterations that immediately follow such injury, but the complex cellular and gene expression changes that determine the ultimate fate of the cell. Both acquired brain injury and degenerative conditions such as Alzheimer?s disease represent an enormous health, social and economic burden. Furthermore, with predictions that Alzheimer?s disease will increase by 3-4 times by the middle of the next century due to the Oaging? of the population, it is becoming even more crucial to establish effective therapeutic interventions. The animal models investigated in this project can be used to unravel the crucial neuronal alterations associated with head trauma and the early stages of Alzheimer?s disease and, more importantly, may be the key to discovering novel strategies to prevent neuronal degeneration in these conditions.Read moreRead less
Investigation Of The Mechanisms Involved In Consolidation Of Memory By Beta 3 Adrenoceptoragonists.
Funder
National Health and Medical Research Council
Funding Amount
$241,018.00
Summary
The inability to form new memories is a major and increasingly prevalent health problem for an aging population. In addition to aging, the inability to form new memories is associated with serious medical conditions including Alzheimer's Disease and diabetes. Common to these conditions is the inability to consolidate memories. Memories are intact for a short while (30 minutes) after the event to be remembered, but memory does not pass on into permanent storage. We have been able to achieve memor ....The inability to form new memories is a major and increasingly prevalent health problem for an aging population. In addition to aging, the inability to form new memories is associated with serious medical conditions including Alzheimer's Disease and diabetes. Common to these conditions is the inability to consolidate memories. Memories are intact for a short while (30 minutes) after the event to be remembered, but memory does not pass on into permanent storage. We have been able to achieve memory consolidation in a particular learning task, which is not normally remembered, by injection of drugs acting on novel receptors (beta 3 adrenoceptors) in the brain of day old chicks. These drugs mimic the action of noradrenaline at beta-3 adrenoceptors. There are a number of ways in which memory consolidation can be enhanced, and we will compare the effects of beta-3 drugs with other potential drugs acting at other types of noradrenaline receptors. One of the actions of beta-3 agonists is related to the uptake of glucose into cells in the brain. We will investigate whether the mechanism of beta-3 enhancement of memory involves the uptake of glucose in brain tissue and studies in cultures of individual cell types will show us which cells are involved. Although this work is done using young chicks, there is no reason to suppose that the basic memory mechanisms at the level of the nerve cell should be different in birds or mammals. There are distinct advantages to using chicks in this research as they can form a long lasting memory for an experience lasting only 10 seconds, and they will discriminate between different colours as part of their learning. This research is aimed at understanding the processes involved in and influencing memory formation. If we are going to develop drugs to alleviate the cognitive problems of old age and more serious cognitive diseases, we need to understand more about the basic mechanisms of memory formation in the normal animal.Read moreRead less