Professor Kay Double

Professor Kay Double, Professor of Neuroscience, The University of Sydney.

Kay Double is Professor of Neuroscience at the Brain and Mind Centre at the University of Sydney where she heads the Neurodegeneration Research Laboratory. Her qualifications include a PhD and the international postdoctoral degree of Habilitation in the field of neurochemistry, that is, the biochemistry of the brain in health and disease. Her work identifies cellular pathways responsible for brain cell death in degenerative disorders, including Parkinson’s disease, motor neurone disease, and dementia disorders, and developing and testing treatments to slow or halt the disease process. Her group recently identified a new type of abnormal protein in Parkinson’s disease which is thought to be associated with brain cell damage. She is also developing novel methods to image disease-associated changes in the brain and spinal cord to improve diagnosis and monitor treatment effects. She leads multidisciplinary, international research groups to meet these challenges in a collaborative manner. In addition to her research awards, she is an award-winning supervisor of Early Career Researchers and students.

Forefront Group:

  • BMC Neurodegeneration Lab Parkinson's Disease Research Group
  • BMC Neurogeneration Lab Motor Neuron Disease Research Group

Affiliate Organisations

The University of Sydney, The University of Melbourne, University of Technology, Sydney, Neuroscience Research Australia, The University of Würzburg, Germany

Neurodegeneration of interest:

Parkinson’s disease, Motor Neurone Disease, Dementia disorders, Ageing

Expertise:

  • Neurodegeneration research
  • Neuroprotection research
  • Development and validation of neuroimaging technologies
  • Neuroscience teaching at undergraduate and graduate level including research student supervision and teaching research

Specific Skills:

  • Neurochemistry
  • Neuropathology
  • Neuroimaging

Specific Skills:

  • Research student positions are available at Honours, Masters or PhD level for the projects below, please contact Prof Double for details.
  • Is nerve cell death in Parkinson disease and motor neurone disease triggered by copper deficiency? CIA.
  • Developing PET-based neuroimaging for copper in the human central nervous system. CIA.
  • The biology of copper and iron in the healthy and diseased human central nervous system. CIA.
  • Who is teaching tertiary neuroscience in Australia? A survey of skills and experience. Joint CI.

Project - Is nerve cell death in Parkinson disease triggered by copper deficiency?

Research Project Abstract

Copper is a vital metal critical for the health and normal function of nerve cells, and a severe deficiency of copper is fatal. Brain diseases that appear to involve a deficiency of copper are more common than previously recognized and include Parkinson disease, motor neurone disease and potentially dementia disorders such as Alzheimer’s disease. We identified a new type of abnormal protein change in the brain in Parkinson disease that involves the copper-requiring protein superoxide dismutase 1 (SOD1). Abnormal forms of SOD1 protein results in nerve cell death in some forms of motor neuron disease. Our work is investigating how this abnormal protein forms in Parkinson disease, the role of copper in the abnormal changes and whether a cellular deficiency in copper is a trigger for nerve cell death in both disorders. We are also testing new treatments to see if we can stop brain cell death by preventing or reducing the formation of this abnormal SOD1 protein. Slowing or preventing brain cell death should benefit patients by slowing the progression of Parkinson disease.

List all Chief investigators and associate investigators

  • CIA: Professor Kay Double, The University of Sydney
  • CIB: Associate Professor Dominic Hare, The University of Melbourne
  • CIC: Professor Rachel Codd, The University of Sydney
  • AI: Associate Professor Peter Crouch, The University of Melbourne
  • AI: Professor Stuart Cordwell, The University of Sydney
  • Research Associate: Dr Benjamin Trist, The University of Sydney
  • Professional staff: Dr Benjamin Rowlands, The University of Sydney
  • Professional staff: Dr Fabian Kreilaus, The University of Sydney
  • Professional staff: Ms Veronica Cottam, The University of Sydney
  • Research students: Mr Amr Abdeen, The University of Sydney
  • Research students: Ms Julia Forkgen, The University of Sydney

Challenges within the field

Parkinson disease involves the progressive death of specific groups of nerve cells, although the reason for the death of these cells is unknown. If we can identify key disease mechanisms that occur early in the disease process, and understand how these early changes result in the eventual death of the nerve cells, we can develop therapies to intervene early in the disease to slow or halt these key processes before nerve cells are damaged.

Research Project Description

Parkinson disease, a common neurodegenerative disorder of movement, develops because of the death of a specific group of brain cells. The cause of the death of these brain cells is not well understood and current treatments for Parkinson disease only provide short-term relief of the movement symptoms but cannot stop or slow the death of these cells. We have discovered that a protein called superoxide dismutase 1 (SOD1) is abnormal in the brains of Parkinson disease patients and we believe that the abnormal protein is involved in the death of the vulnerable brain cells. Interestingly, another abnormal form of this same protein results in nerve cell death in a type of another degenerative disease amyotrophic lateral sclerosis (ALS). To reveal how the abnormal protein is formed we are examining the abnormal SOD1 in post mortem brain tissues from Parkinson disease patients to characterise how it is altered. We have also developed a unique mouse model of Parkinson’s disease that also forms this abnormal protein in the brain and we can use this model to examine the molecular changes that lead to the altered protein. We are investigating treatments used in other diseases that we believe may be able to reduce the formation of the abnormal protein and decrease cell damage. If we are correct, we will not only know why brain cells die in Parkinson disease, but will also have a treatment for slowing or even halting the disease.

The approaches we are using in this project include neuropathology, studying the interactions between protein and metals using mass spectroscopy and synchrotron technologies, determining levels of total and subtypes of proteins using protein isolation and quantification using gel electrophoresis, post mortem human brain studies and preclinical animal model studies.

Funding for this work
NHMRC Ideas grant APP1181864: Superoxide dismutase one dysfunction: a novel pathogenic mechanism in Parkinson disease. 2020-2022, CIA.

Michael J. Fox Foundation, USA grant: Does dopamine cell death result from a novel proteinopathy in Parkinson’s disease brain? 2019-2021, CIA

Research Objectives

  • To identify the cellular pathways leading to the death of the vulnerable nerve cells and to identify key points within those pathways that represent targets for the development of treatments which aim to slow or halt cell death.
  • To identify and test novel disease-modifying compounds.
  • To develop better tools to support earlier and more accurate diagnostic methods for Parkinson disease.
  • Our ultimate aim to develop treatments that stop the development of clinical Parkinson disease, thereby achieving disease prevention.

Key Publications from this project

  • Trist B, Hilton JB, Crouch PJ, Hare DJ, Double KL. (2020) Superoxide dismutase 1 in health and disease: How a front-line antioxidant becomes neurotoxic. Angew. Chem. Int. Ed. 59, 2-34. doi: 10.1002/anie.202000451.
  • Genoud, S., Alistair M. Senior, A.M., Dominic J. Hare, D.J., Double, K.L. (2020) Copper and iron levels in Parkinson’s disease brain and biofluids: A meta-analysis. Mov Disord, 35: 662-671. doi:10.1002/mds.27947
  • Trist, B.G., Hare, D.J., Double, K.L. (2018) A proposed mechanism for neurodegeneration in movement disorders characterized by metal dyshomeostasis and oxidative stress. Cell Chem Bio. 25(7):807-816. doi:10.1016/j.chembiol.2018.05.004.
  • Trist, B.G., Fifita, J.A., Freckleton, S.E., Hare, D.J., Lewis, S.J.G., Halliday, G.M., Blair, I.P., Double, K.L. (2018) Accumulation of dysfunctional SOD1 protein in Parkinson’s disease is not associated with mutations in the SOD1 gene. Acta Neuropathol. 135(1):155-146. doi:10.1007/s00401-017-1779-6. 
  • Trist, B.G., Davies, K.M., Cottam, V., Genoud, S., Ortega, R., Roudeau, S., Carmona, A., De Silva, K., Wasigner, V., Lewis, S.J.G., Sachdev, P., Smith, B., Troakes, C., Vance, C., Shaw, C., Al-Sarraj, S., Ball, H., Halliday, G., Hare, D.J., Double, K.L. (2017) Amyotrophic lateral sclerosis-like superoxide dismutase 1 proteinopathy is associated with neuronal loss in Parkinson’s disease brain. Acta Neuropathol. 134(1):113-127. doi:10.1007/s00401-017-1726-6

Infographic / Medical Diagram / Scientific Diagram / Picture

Key Findings

  • We have identified a new type of abnormal protein associated with nerve cell loss that represents a shared pathway to nerve cell damage in both Parkinson disease and motor neurone disease.
  • We are exploring how this abnormal protein forms in the Parkinson disease brain and novel approaches to prevent its formation to prevent cell death. We are also testing whether treatments currently in use for other disorders can prevent this abnormal protein from forming.
  • Our work has discovered the first link between disease processes in Parkinson disease and motor neurone disease. This has increased our understanding of both of these disorders. We hope this finding will allow us to develop more effective treatments for current patients and, in future, to achieve disease prevention.