Targeting inflammatory mechanisms in Alzheimer's disease. [ 2004 - 2006 ]

Research Grant

Researchers: Dr Claire Shepherd (Principal investigator) ,  A/Pr Mark Raftery ,  E/Pr Carolyn Geczy ,  Prof Gary Halliday

Brief description Alzheimer s disease accounts for the majority of dementia cases and is the most common cause for nursing home requirements in Australia. It is not a disease that is confined to old age as it can also affect individuals in their 20s and 30s. There is currently no cure for Alzheimer's disease, largely because the underlying cause is unknown. Deposition of the amyloid-beta protein within the brain of Alzheimer's disease patients is thought to be responsible for the neuronal cell loss which underlies the dementia. However, amyloid-beta protein deposition can occur in the absence of dementia and in the asbence of significant neuronal cell loss, suggesting that an alternative mechanism of neurotoxicity exists. Inflammation is a consistent feature of the Alzheimer's disease brain. We have preliminary evidence to suggest that inflammation is responsible for the neurotoxicity in Alzheimer's disease. We have recently observed a significant inflammatory response surrounding an unidentified protein in the brains of individuals with a familial form of Alzheimer's disease due to a genetic mutation. This inflammatory response is not associated with the significant amyloid-beta protein deposition seen in these cases suggesting that a novel potent inflammatory stimulus exists. Furthermore, these cases have greater neuronal cell loss and a shorter disease duration, both indicators of increased neurotoxicity. The present study is designed to determine the toxicity of inflammation and the stimulus driving this response in the Alzheimer's disease brain using tools for protein and gene analysis, as well as determining the extent of inflammation-mediated toxicity on neuronal cells grown in culture. Only by addressing these aims can we concentrate on developing safe and effective therapeutic strategies to prevent or treat the disease process.

Funding Amount $AUD 392,750.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant