The University of Sydney
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Sir Zelman Cowen Universities Fund Alzheimer's Disease Research Grant

Since its establishment in 1978, the Sir Zelman Cowen Universities Fund has raised funds for medical and scientific research focused on finding therapies for still-incurable diseases. The work supported by the Fund is carried out at the University of Sydney and the Hebrew University of Jerusalem.

Since the launch of its Alzheimer's Disease & Inflammation Initiative in 1996, the Fund has supported research aimed at finding the cause and a potential cure, for the dementia of Alzheimer's disease (AD).

Following this interest, in May 2008, the Trustees of the Fund announced the establishment of the Sir Zelman Cowen Universities Fund Alzheimer's Disease Research Grant for a research project in the field of Alzheimer's disease, where the aim of the project is to develop and/or assess new treatments for this condition. A call for applications was also made at this time to permanent members of staff of the University of Sydney and the Hebrew University of Jerusalem. Joint applications for cooperative projects between permanent members of staff of both universities were also welcomed.

In September 2008 the Trustees of the Fund announced the award of the grant of $100,000 over 2 years to Dr Claire Goldsbury, Brain & Mind Research Institute, University of Sydney and Dr Karen Cullen, Discipline of Anatomy & Histology, University of Sydney for their project entitled, Energy deficiency as a cause of neuritic pathology in Alzheimer's Disease.

Dr Claire Goldsbury & Dr Karen Cullen

Summary of the Project:
Alzheimer's disease (AD) progressively destroys brain cells involved in memory functions. One of the diagnostic abnormalities of the damaged nerve cells is their accumulation of a protein called tau. Tau inclusions may contribute to nerve cell dysfunction by blocking trafficking of important components to synapses. Loss of synapses underlies the memory loss central to the disease. This project focuses on the process that causes the accumulation of tau. Understanding this process is important for identifying and developing new ways to treat AD.

Decline in energy metabolism, visible in AD brain scans occurs in the same areas as damaged nerve cells. The hypothesis on which this project is based is that reduced energy metabolism in the brain initiates the accumulation of tau. Using a multi-pronged approach, this study aims to determine ways to short-circuit the pathway between energy depletion and brain damage by revealing the sequence of events that explains the abnormal accumulation of tau.

For further information about the AD Grant and this project, please contact the Fund's office.

Final Report

 

Work commenced on the joint project in 2009 and was briefly interrupted by a period of maternity leave for Dr Goldsbury. The final report was submitted in late 2012 .
The project set out to achieve a better understanding of the process that causes the accumulation of a protein called tau in the brains of AD sufferers. An accumulation of tau is one of the diagnostic abnormalities of the damaged nerve cells in AD. It may contribute to nerve cell dysfunction by blocking trafficking of important components to synapses. Loss of synapses underlies the memory loss central to the disease.
Reporting on the project, Dr Goldsbury wrote, “In this project supported by the SZCUF, we have demonstrated that reduced energy metabolism by inhibition of mitochondrial function in cultured neurons gives rise to the redistribution of tau and cofilin into rod-like structures that appear to mimic those in the AD brain. Further, we demonstrated that the density of cofilin rods in human AD brains is significantly higher than in normal aged human brain. However, we also showed that some aged normal brains contained low levels of cofilin rods, although these brains were devoid of abnormal tau. This suggests that cofilin rod generation may be an early event in the neurodegenerative cascade representing a possible early-stage mechanism in the progression to AD dementia and therefore an ideal future target for therapeutic intervention that might be useful in treatment of neurological diseases. Unexpectedly, however, despite an extensive study, we were not able to show any substantial microscopic overlap of tau and cofilin in the human AD brain. We conclude that the abnormalities involving cofilin and tau probably occur in parallel in different types of brain cells. This is a significant finding as it will direct future work that highlights the important role of non-neuronal cells in the mechanism of neuronal cell death in the AD brain. The work we performed with the SZCUF grant resulted in 4 publications in highly ranked international journals (3 published, and 1 soon to be submitted) demonstrating a significant contribution to the AD research field.”

For further information about the AD Grant and this project, please contact the office.