Gene-environment Interaction In Healthy Brain Ageing And Age Related Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$2,162,805.00
Summary
Healthy ageing is characterised by low level of disability, high cognitive and functional capacity, and an active engagement in life. The most important ingredient of healthy ageing is a healthy brain, bereft of age-related diseases and dysfunction. Brain ageing and brain diseases are determined by multiple genetic factors that interact with environmental influences. The genes are multiple, the majority of which have a small influence. This study is an attempt to identify some of these genes and ....Healthy ageing is characterised by low level of disability, high cognitive and functional capacity, and an active engagement in life. The most important ingredient of healthy ageing is a healthy brain, bereft of age-related diseases and dysfunction. Brain ageing and brain diseases are determined by multiple genetic factors that interact with environmental influences. The genes are multiple, the majority of which have a small influence. This study is an attempt to identify some of these genes and investigate their interactions with environmental factors. It will use a unique resource, the NHMRC Australian Twin Registry (ATR) to identify elderly twins, and will also include the siblings of these twins so as to increase the ability to identify the important factors. The participants, who are listed on the ATR and recruited from NSW, Queensland and Victoria, will receive detailed neurological, psychiatric and cognitive assessments, and will undergo brain MRI scans. Their blood samples will be used to measure key chemicals that may affect brain ageing and to extract DNA for genetic tests. They will be followed-up every two years thereafter, and changes in their brain structure and cognitive functioning will be examined. Available statistical models will be used to examine gene-environment interactions and specific genes will be explored for their contribution to the additive genetic effects. This study will yield an important resource for national and international collaborations and has the potential to discover new genes.Read moreRead less
Diabetes And Dementia: Studies With The Fremantle Diabetes Study Cohort.
Funder
National Health and Medical Research Council
Funding Amount
$315,509.00
Summary
Dementia is an extremely serious condition which affects a large proportion of the older population. Recent evidence has shown that diabetes, which is another common condition in the elderly, doubles the risk of an older person developing Alzheimer's disease and other forms of dementia. Why this happens is unknown but insulin therapy has been highlighted as a possible cause. As many older people are on insulin for their diabetes, it is extremely important to confirm or refute this finding. It se ....Dementia is an extremely serious condition which affects a large proportion of the older population. Recent evidence has shown that diabetes, which is another common condition in the elderly, doubles the risk of an older person developing Alzheimer's disease and other forms of dementia. Why this happens is unknown but insulin therapy has been highlighted as a possible cause. As many older people are on insulin for their diabetes, it is extremely important to confirm or refute this finding. It seems possible that insulin may not be the direct cause but that some other associated factor such as poor diabetes control, recurrent hypoglycaemic attacks or cerebrovascular disease causes dementia. On theoretical grounds, Alzheimer's disease may have a vascular basis. If Alzheimer's disease was, in part, caused by vascular disease then there is the potential to prevent cases of dementia developing by paying attention to the known risk factors for vascular disease such as hypertension. The Fremantle Diabetes Study is an ideal group of community living diabetic individuals in which we can study whether some or all of these factors cause Alzheimer's disease or dementia and gain insights into the potential for prevention.Read moreRead less
The Role Of Oxidative Stress In The Patho-aetiology Of Prion Disorders Using Infected Cell Culture And Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$112,014.00
Summary
The transmissible spongiform encephalopathies (TSE; also known as prion diseases) are a biologically unique and fascinating group of invariably fatal diseases which primarily affect the brains of both humans and animals. In humans, sporadic Creutzfeldt-Jakob disease (CJD) is the most common form, while in animals it is the recent epidemic of bovine spongiform encephalopathy (mad cow disease), and its probable transmission to humans as new variant CJD, which has drawn so much attention to this gr ....The transmissible spongiform encephalopathies (TSE; also known as prion diseases) are a biologically unique and fascinating group of invariably fatal diseases which primarily affect the brains of both humans and animals. In humans, sporadic Creutzfeldt-Jakob disease (CJD) is the most common form, while in animals it is the recent epidemic of bovine spongiform encephalopathy (mad cow disease), and its probable transmission to humans as new variant CJD, which has drawn so much attention to this group of disorders. The preponderance of scientific evidence now supports the belief that infectivity in TSEs relates predominantly (probably exclusively) to a protein (called the prion protein; PrP) which is normally found on the cell surface of a number of types of brain cells, including neurons. Transmissibility, and hence infectivity, is more correctly associated with a malfolded version of PrP into an abnormal shape which gives the mutant protein significantly different biological and biochemical properties, including relative resistance to breakdown by enzymes that metabolise proteins (proteases) and enhanced tendency to aggregate. However, the precise steps involved in this transformation to the abnormal infectious form of PrP are not known. Similarly, our understanding of how different folding and accumulation of this protein brings about disease is not clear. Nevertheless, as with other neurological diseases (eg Alzheimer's disease) which are a consequence of unexplained spontaneous premature degeneration of parts of the brain (neurodegenerative diseases), oxidative stress is increasingly believed to play a role. Oxidative stress is a generic term used to describe the enhanced production within a cell of small, very harmful, oxygen containing molecules which under normal circumstances can be successfully detoxified. This project involves a detailed study of the role of oxidative stress in the causation of prion diseases using both mouse and cell culture models.Read moreRead less