DUAL AND MULTIPLE PROTEINOPATHIES IN NEURODEGENERATIVE DEMENTIAS – RISK FACTORS, PROGNOSTIC INDICATORS AND CLINICAL RAMIFICATIONS
Funder
National Health and Medical Research Council
Funding Amount
$604,644.00
Summary
Dementia is the umbrella term used to refer to a number of different clinical presentations,each associated with distinct histopathological signatures of protein aggregates and spread.However, converging evidence now suggests the common co-occurences of dual/multiple proteinopathies across dementia syndromes.The present study will identify the clinical ramifications and factors that are most predictive for such proteinopathies in a large cohort of longitudinally-studied patients with dementia.
Finding Clinical Predictors For The Underlying Pathology In Different Frontotemporal Dementia (FTD) Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$136,593.00
Summary
Due to the ageing population in Australia it is predicted that the prevalence of dementia will increase four-fold by 2050. Developing disease-modifying therapies for dementia is therefore a priority, however we also need to be able to accurately identify patients for whom these therapies will be beneficial. Here we will develop strategies for identifying patients with particular protein abnormalities in their brain, the substrate of most therapeutic interventions.
In Vivo Tau Imaging In Alzheimer’s Disease And Other Dementias
Funder
National Health and Medical Research Council
Funding Amount
$538,998.00
Summary
Alteration of the normal protein tau leads to its deposition inside the brain cells leading to their death. These deposits have been well characterized and they are associated with cognitive impairment. We propose to study tau deposits in vivo in humans using positron emission tomography (PET) and assess its association with cognition and other signs of neurodegeneration
Characterisation Of Eating Behaviour And Metabolic Phenotypes Across Neurodegenerative Diseases: Insights For Survival And Progression
Funder
National Health and Medical Research Council
Funding Amount
$340,891.00
Summary
It has been suggested that metabolic changes and eating behavior could modify the progression of neurodegeneration. This research aims using brain imaging, pathological examination and novel techniques from obesity research to examine if there are characteristic metabolic changes in patients with frontotemporal dementia, Amyotrophic lateral sclerosis and Alzheimer’s disease; how these changes relate to eating behavior, and how they may affect disease progression and survival.
SELECTIVE VULNERABILITY IN ALZHEIMER’S DISEASE AND RELATED DISORDERS: MECHANISM OF TAU PATHOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$1,072,324.00
Summary
Alzheimer’s disease and related dementias affect 230,000 people in Australia, with numbers expected to grow to 730,000 by 2050. The direct costs for health and residential care alone exceed $6.6 billion per annum. By identifying genes that protect degenerating neurons in the Alzheimer brain, a deeper understanding of the underlying processes will be gained and therapeutic targets will be defined that will assist in developing a therapy for a yet uncurable disease.
Role Of Apolipoprotein D In Alzheimer's Disease And Frontotemporal Dementia
Funder
National Health and Medical Research Council
Funding Amount
$575,612.00
Summary
ApoD is a highly conserved lipocalin known for its antioxidant nature and role in regulation of inflammation. Oxidative stress and neuroinflammation are known to play a critical role in dementia. This project will study the association of apoD to inflammatory and oxidative stress markers in Alzheimer’s disease and Frontotemporal Dementia, two major forms of dementia. It will also examine the impact of apoD on disease pathology. Hence this project will lead us to therapeutic potentials of apoD.
This research proposal outlines studies aimed at identifying specific biomarkers of neurodegeneration. Given the complexity and clinical overlap of these disorders the identification of diagnostic biomarkers for their early detection is crucial; especially in the identification of at-risk individuals before the development of symptoms. This will allow early intervention with disease-modifying medications which by arresting neuronal loss would prevent or delay onset of the disease.
NOVEL MECHANISMS UNDERLYING THE SPREADING OF TAU PATHOLOGY IN ALZHEIMER’S DISEASE AND OTHER TAUOPATHIES
Funder
National Health and Medical Research Council
Funding Amount
$640,106.00
Summary
Alzheimer’s disease and related dementias affect 230,000 people in Australia, with numbers expected to grow to three times that by 2050. The direct costs for health and residential care alone already exceed $6.6 billion per annum. The underlying pathomechanisms and the processes that drive the progression of neurodegeneration in these devastating disorders remain largely unknown. Here, we will identify novel therapeutic targets and assist in developing therapies for yet incurable diseases.
Brain Connectivity Biomarkers Predict Specific Memory Consolidation Deficits Across Dementia Subtypes
Funder
National Health and Medical Research Council
Funding Amount
$83,149.00
Summary
With the increasing ageing population there is expected to be a significant increase in the number of dementia cases in the near future. This project aims to improve the accuracy of existing diagnostic protocols for dementia by combining recent advances in magnetic resonance imaging with traditional cognitive assessments. We expect the outcome to improve detection in the early stages of disease onset so that patients may receive immediate medical treatment.
Alzheimer's Disease And Related Disorders: Mechanism Of Tau Pathology In Established And Novel Transgenic Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$423,017.00
Summary
Alzheimer's disease (AD) is a devastating neurodegenerative disease for which no cure is available. It affects more than 15 million people worldwide. There are estimates that by 2040, approximately 500'000 Australians will suffer from AD, with associated health costs of about 3% of the GDP. AD is characterized by two major brain lesions, beta-amyloid plaques and neurofibrillary tangles (NFTs). The latter contain a protein called tau which is in a fibrillar and highly phosphorylated state. We wer ....Alzheimer's disease (AD) is a devastating neurodegenerative disease for which no cure is available. It affects more than 15 million people worldwide. There are estimates that by 2040, approximately 500'000 Australians will suffer from AD, with associated health costs of about 3% of the GDP. AD is characterized by two major brain lesions, beta-amyloid plaques and neurofibrillary tangles (NFTs). The latter contain a protein called tau which is in a fibrillar and highly phosphorylated state. We were the first to establish a transgenic animal model of pre-tangles and, together with Dr. Hutton's laboratory, of NFT formation. We could further show that injections of beta-amyloid into brains of our tau mutant mice enhanced the NFT pathology in these mice. By Functional Genomics we identied genes and proteins, which are induced by tau expression. The specific aim of this proposal is to determine whether oxidative stress enhances the tau pathology in our tau mutant mice and whether distinct brain areas are particularly susceptible to this kind of stress. The reason for addressing this question is twofold: On the one hand, we have found in our mice that reactive oxygen species are increased, secondly it is known that some brain areas in the AD brain are degenerating, whereas others are not. A second aim is to develop novel tau transgenic models where individual interactions of tau with cellular proteins are disturbed. Finally, we want to determine whether the two kinases BMX and FAK and the phosphatase PPV regulate tau phosphorylation in vivo. Together, we hope that our efforts lead to a better understanding of the pathogenic mechanisms in AD and related disorders. As pathocascades are likely to be shared between a range of diseases, these findings may also contribute to other fields of research, such as Parkinson's disease. Ultimately, these efforts will assist in the development of a safe treatment of AD.Read moreRead less