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Research Topic : Cognitive dysfunction
Australian State/Territory : WA
Scheme : NHMRC Project Grants
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  • Funded Activity

    Characterization Of Novel Regulators Of Erythropoiesis

    Funder
    National Health and Medical Research Council
    Funding Amount
    $437,545.00
    Summary
    Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature fu .... Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature functional cells. We have identified six molecules which interact with Lyn in red blood cells. We have shown that amolecule called HS1 is important for epo function in individual red blood cells and now we plan to investigate its functions in whole animals, including mice that lack the HS1 gene. We have also shown that a molecule called Trip1 is important for red blood cell development. Interestingly, this molecule also interacts with the thyroid hormone receptor and can influence the effects of epo and thyroid hormone on red blood cell development. The interplay between these two hormones will be looked at in more detail both at the cell and whole animal levels in normal mice and those lacking the thyroid hormone receptor gene. The third Lyn binding molecule we isolated is a novel gene-we have named it ankyrin repeat protein in line with the molecules it is related to. This gene is expressed in red blood cells and we aim to investigate what role it plays in the development of these cells. The fourth gene is also novel and is closely related to another called AFAP-110, which can exert effects on the structure of a cell. Its role in red blood cell structure will also be investigated. Finally, the last two molecule we have identified are both novel and are unrelated to any other known proteins. As above, the effects of these two molecules on red blood cell development will be investigated.
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    Funded Activity

    Aspirin For The Prevention Of Cognitive Decline In The Elderly: A Neuro-Vascular Imaging Study (ENVIS-ion) From ASPREE

    Funder
    National Health and Medical Research Council
    Funding Amount
    $1,341,232.00
    Summary
    The ENVIS-ion trial will examine whether Aspirin is effective in delaying the onset of worsening of thinking and memory abilities in healthy older adults. Magnetic resonance imaging (MRI) of brain structure will detect markers of early worsening of thinking and memory abilities. Blood vessels in the back of the eye (retina) share many features with vessels in the brain. We will compare whether aspirin lessens changes over time of features shown with brain MRI and retinal photography.
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    Funded Activity

    Predicting Health And Disease In Australian Men Over The Age Of 80 Years - The Health In Men Study

    Funder
    National Health and Medical Research Council
    Funding Amount
    $528,754.00
    Summary
    Australia is ageing rapidly but we still do not know whether the risk factors, such as health and lifestyle, that predict ill health in middle aged people, apply to people as they reach old age. This study of a large group of older men will examine the type and level of risk factors that apply to men aged beyond 75 years. It will not only determine rates of disability and mortality but also health service outcomes, including hospitalisation, and residential and community care usage.
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    Funded Activity

    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.
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