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
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
Effects Of Latrepirdine On Beta Amyloid Clearance, Aggregation And Neurodegeneration In Alzheimer�s Disease
Funder
National Health and Medical Research Council
Funding Amount
$512,647.00
Summary
Alzheimer's disease (AD) is becoming more common with our growing aged population and currently no treatment exists that halts disease progress. The increasing health costs of AD underscore the need for development of any treatment that will slow or halt AD pathogenesis. By understanding the mechanisms of action of a drug [latrepirdine] that has recently shown some promise in phase II clinical trials, related drugs that are more specific and potent will be developed.
The Effect Of Human ApoE Isoforms And ApoE Receptors On The Clearance Of Oligomeric A 42 By Hepatocytes In Vitro
Funder
National Health and Medical Research Council
Funding Amount
$424,801.00
Summary
Alzheimer's disease (AD) is a progressive memory disorder. Increased production of a short peptide called amyloid- (A ) aggregates to form the sticky masses in the brains of AD patients. The amount of A in the brain is a balance between production and clearance. Surprisingly, we recently demonstrated that the liver clears the majority of A . These results connect AD and cardiovascular disease (CVD), enabling current CVD therapeutics to target A clearance by the liver.
TELEPHONE COUNSELLING FOR MAINTENANCE OF PHYSICAL ACTIVITY, WEIGHT LOSS And GLYCAEMIC CONTROL IN TYPE 2 DIABETES
Funder
National Health and Medical Research Council
Funding Amount
$1,285,894.00
Summary
Regular exercise, a healthy diet and weight loss are key to managing type 2 diabetes, yet these are major challenges for most people with diabetes. This study will evaluate the impact of a telephone counselling program to assist people with type 2 diabetes to exercise, eat a healthy diet and lose weight, with the goal of helping them to sustain these changes over the long-term. It is expected that these lifestyle changes will also result in improved blood glucose control and quality of life.
Alpha-2-Macroglobulin And The Transport And Uptake Of The Hormone, Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Hepcidin is a peptide hormone that is a major regulator of iron metabolism. It has been suggested that hepcidin is free in the blood. However, we recently identified that hepcidin binds with alpha-2-macroglobulin (a2-M) in the plasma and this increases the efficacy of this peptide. The demonstration that a2-M plays a role in hepcidin biology will lead to a better understanding of hepcidin physiology, the development of methods for its measurement and improved treatment of iron related diseases.
Understanding The Acute And Cumulative Metabolic Effects Of Prolonged Sitting In Adults
Funder
National Health and Medical Research Council
Funding Amount
$416,597.00
Summary
Sedentary behaviour (sitting time) has been linked to an increased risk of chronic illnesses, including type 2 diabetes and obesity, but recent evidence suggests that light-intensity activity (non-exercise activities of daily living) is associated with reduced risk. These studies will examine whether breaking up sitting time with frequent short periods of activity can overcome the negative effects of prolonged sitting on blood glucose and blood fats in overweight older adults.
A Behavioural Intervention For The Adoption & Maintenance Of Physical Activity In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$334,955.00
Summary
For people with type 2 diabetes (T2DM) it is essential that blood glucose levels are managed well to reduce the risk of developing complications. Physical activity is essential for maintaining glucose levels because it helps make the muscles use glucose more effectively. In particular, being active through strength training not only improves blood glucose levels, but can be very effective for maintaining good physical functioning, which is known to be reduced by having T2DM. This study builds on ....For people with type 2 diabetes (T2DM) it is essential that blood glucose levels are managed well to reduce the risk of developing complications. Physical activity is essential for maintaining glucose levels because it helps make the muscles use glucose more effectively. In particular, being active through strength training not only improves blood glucose levels, but can be very effective for maintaining good physical functioning, which is known to be reduced by having T2DM. This study builds on our earlier research which demonstrated significantly improved blood glucose levels from a strength training program for older adults with T2DM. The strength training program is to be administered nationally in a research to practice trial (Lift for Life); however, the original research found that those who did not complete the program as it was intended (ie, poor adherence) did not show significant improvements in blood glucose levels. Furthermore, maintenance of strength training exercises after completion of the program was poor and resulted in return of blood glucose levels back to pre-starting levels. In people without diabetes, we have collected pilot data that shows that the use of behavioural strategies based on behavioural theories whereby each person's motivations and barriers are taken into consideration is more effective than the traditional one-treatment-fits-all approach. This study will evaluate the effectiveness of using behavioural strategies for improving adherence and maintenance to the Lift for Life strength training program (Enhanced L4L) for older adults with T2DM compared with the Standard L4L program. It will also follow-up participants 6 months later to determine the extent to which the changes in behaviour can be maintained. The study will provide information that will assist in the design, delivery and uptake of programs to improve treatment strategies in older adults with T2DM through the maintenance of healthier behaviours and lifestyles.Read moreRead less