People_

Professor Kay Double

Professor
Brain and Mind Centre and Theme of Neuroscience, School of Medical Sciences

Phone

+61 2 9114 4292

Email

[email protected]

Details

Member of the Brain and Mind Centre

Research interests

I work at the interface betweenneuropathological(human tissue) research and quantitative neurochemistry, using these skills to investigate disease mechanisms in Parkinson’s disease. This human-based approach for identifying disease mechanisms is critically important in this disorder, as unlike some other neurodegenerative diseases, Parkinson’s disease only occurs in the human. Funded by an international Research Fellowship (Alexander von Humboldt Foundation, Germany) and then consecutive federal Australian Research Fellowships and federal grant funding, I demonstrated that neuromelanin, the pigment which characterises the vulnerable cells in the Parkinson’s disease brain, plays an active neuroprotective role in healthy dopaminergic cells. This changed the then dogma that neuromelanin pigment has a negative impact upon the healthy brain. I then demonstrated abnormal changes in neuromelanin, and associated cellular metals, reflecting the pattern of brain cell death in Parkinson’s disease, indicating that changes in this metal-binding molecule may play a role in the etiology of Parkinson’s disease. This prompted me to investigate other metal-binding proteins in Parkinson’s disease and led to the discovery of SOD1 proteinopathy associated with neuronal death in Parkinson’s disease brain, and the similarities between this pathology and the well-documented SOD1 proteinopathy present in post mortem spinal cord from patients with familial amyotrophic lateral sclerosis.

Current projects

The role of copper dyshomeostasis and dysfunctional copper-binding (cupro)proteins in Parkinson's disease aetiology
Validating molecular pathways of superoxide dismutase 1 (SOD1) neurotoxicity in amyotrophic lateral sclerosis patients

Themes

Neurosciences and Mental Health

Keywords

Biochemistry, Molecular biology, Motor neuron disease, Parkinson's disease, Therapeutics

Approaches

Aetiology, Pathology, Translational Research

Current research students

Project title	Research student
Investigation of Biomarkers of Neurodegenerative Disease	Anne LI

Selected publications

Neuropyschiatric disorders: an integrative approach. J. Neural Trans. Suppl 72

(Springer, 2007)

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Edited Books

Gerlach, M., Deckert, J., Double, K., Koutsilieri, E. (2007). Neuropyschiatric disorders: an integrative approach. J. Neural Trans. Suppl 72. New York: Springer.

Book Chapters

Dickson, P., Shehadeh, J., Double, K., Bobrovskaya, L., Reyes, S., Dunkley, P., Halliday, G. (2013). Analysis of Tyrosine Hydroxylase Isoforms and Phosphorylation in Parkinson's Disease. In Lee E. Eiden (Eds.), Catecholamine Research in the 21st Century: Abstracts and Graphical Abstracts, 10th International Catecholamine Symposium, 2012, (pp. 15-15). London: Elsevier. [More Information]
Double, K., Finberg, J. (2013). Parkinson's Disease. In Donald W. Pfaff (Eds.), Neuroscience in the 21st Century: From Basic to Clinical, (pp. 2903-2921). New York: Springer.
Halliday, G., Reyes, S., Double, K. (2012). Substantia Nigra, Ventral Tegmental Area, and Retrorubral Fields. In Juergen K. Mai and George Paxinos (Eds.), The Human Nervous System, (pp. 439-455). London: Academic Press. [More Information]
Double, K., Maruyama, W., Naoi, M., Gerlach, M., Riederer, P. (2011). Biological Role of Neuromelanin in the Human Brain and Its Importance in Parkinson's Disease. In Jan Borovansky, Patrick A. Riley (Eds.), Melanins and Melanosomes: Biosynthesis, Biogenesis, Physiological, and Pathological Functions, (pp. 225-246). Weinheim, Germany: Wiley - V C H Verlag GmbH & Co. KGaA.

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Journals

Zhu, J., Graziotto, M., Cottam, V., Hawtrey, T., Adair, L., Trist, B., Pham, T., Rouaen, J., Ohno, C., Heisler, M., Double, K., New, E., et al (2024). Near-Infrared Ratiometric Fluorescent Probe for Detecting Endogenous Cu2+ in the Brain. ACS Sensors, 9(6), 2858-2868. [More Information]
Penning, L., Berenguer, M., Czlonkowska, A., Double, K., Dusek, P., Espinós, C., Lutsenko, S., Medici, V., Papenthin, W., Stremmel, W., et al (2023). A Century of Progress on Wilson Disease and the Enduring Challenges of Genetics, Diagnosis, and Treatment. Biomedicines, 11(2). [More Information]
Todd, G., Rae, C., Taylor, J., Rogasch, N., Butler, J., Hayes, M., Wilcox, R., Gandevia, S., Aoun, K., Esterman, A., Lewis, S., Matar, E., Double, K., et al (2023). Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity. Journal of Neuroscience Research, 101(2), 263-277. [More Information]
Diong, J., Bero, L., Double, K., Ong, Y. (2023). Responsible research practices could be more strongly endorsed by Australian university codes of research conduct. Research Integrity and Peer Review.
Foley, P., Hare, D., Double, K. (2022). A brief history of brain iron accumulation in Parkinson disease and related disorders. Journal of Neural Transmission, 129(2023-06-05 00:00:00), 505-520. [More Information]
Trist, B., Genoud, S., Roudeau, S., Rookyard, A., Abdeen, A., Cottam, V., Hare, D., White, M., Altvater, J., Fifita, J., Cordwell, S., Halliday, G., Double, K., et al (2022). Altered SOD1 maturation and post-translational modification in amyotrophic lateral sclerosis spinal cord. Brain, 145(9), 3108-3130. [More Information]
Trist, B., Fifita, J., Hogan, A., Grima, N., Smith, B., Troakes, C., Vance, C., Shaw, C., Al-Sarraj, S., Blair, I., Double, K. (2022). Co-deposition of SOD1, TDP-43 and p62 proteinopathies in ALS: evidence for multifaceted pathways underlying neurodegeneration. Acta Neuropathologica Communications, 10(1). [More Information]
Abdeen, A., Trist, B., Double, K. (2022). Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis. NPJ Parkinson's Disease, 8(1). [More Information]
John, A., Singh, A., Nguyen Do, T., Eidels, A., Nalivaiko, E., Gavgani, A., Brown, S., Bennett, M., Lal, S., Simpson, A., Double, K., Kleitman, S., et al (2022). Unravelling the Physiological Correlates of Mental Workload Variations in Tracking and Collision Prediction Tasks. IEEE Transactions on Neural Systems and Rehabilitation Engineering, 30, 770-781. [More Information]
Aoun, K., Double, K., Pearson-Dennett, V., Yilmaz, R., Berg, D., Todd, G. (2021). Measurement of the adult human midbrain with transcranial ultrasound. PloS One, 16, e0247920. [More Information]
Roudeau, S., Trist, B., Carmona, A., Davies, K., Halliday, G., Rufin, Y., Claverol, S., Van Malderen, S., Falkenberg, G., Double, K., et al (2021). Native Separation and Metallation Analysis of SOD1 Protein from the Human Central Nervous System: A Methodological Workflow. Analytical Chemistry, 93(32), 11108-11115. [More Information]
Trist, B., Hilton, J., Hare, D., Crouch, P., Double, K. (2021). Superoxide Dismutase 1 in Health and Disease: How a Frontline Antioxidant Becomes Neurotoxic. Angewandte Chemie - International Edition, 60(17), 9215-9246. [More Information]
Genoud, S., Senior, A., Hare, D., Double, K. (2020). Meta-Analysis of Copper and Iron in Parkinson's Disease Brain and Biofluids. Movement Disorders, 35(4), 662-671. [More Information]
Genoud, S., Jones, M., Trist, B., Deng, J., Chen, S., Hare, D., Double, K. (2020). Simultaneous structural and elemental nano-imaging of human brain tissue. Chemical Science, 11(33), 8919-8927. [More Information]
Shehadeh, J., Double, K., Murphy, K., Bobrovskaya, L., Reyes, S., Dunkley, P., Halliday, G., Dickson, P. (2019). Expression of tyrosine hydroxylase isoforms and phosphorylation at serine 40 in the human nigrostriatal system in Parkinson's disease. Neurobiology of Disease, 130, 1-8. [More Information]
Virachit, S., Mathews, K., Cottam, V., Werry, E., Galli, E., Rappou, E., Lindholm, P., Saarma, M., Halliday, G., Shannon Weickert, C., Double, K. (2019). Levels of glial cell line-derived neurotrophic factor are decreased, but fibroblast growth factor 2 and cerebral dopamine neurotrophic factor are increased in the hippocampus in Parkinson's disease. Brain Pathology, 29(6), 813-825. [More Information]
Trist, B., Hare, D., Double, K. (2019). Oxidative stress in the aging substantia nigra and the etiology of Parkinson's disease. Aging Cell, 18(6), 1-23. [More Information]
Weissleder, C., Barry, G., Fung, S., Wong, M., Double, K., Webster, M., Weickert, C. (2019). Reduction in IGF1 mRNA in the Human Subependymal Zone During Aging. Aging and Disease, 10(1), 197-204. [More Information]
Trist, B., Hare, D., Double, K. (2018). A Proposed Mechanism for Neurodegeneration in Movement Disorders Characterized by Metal Dyshomeostasis and Oxidative Stress. Cell Chemical Biology, 25(7), 807-816. [More Information]
Trist, B., Fifita, J., Freckleton, S., Hare, D., Lewis, S., Halliday, G., Blair, I., Double, K. (2018). Accumulation of dysfunctional SOD1 protein in Parkinson's disease is not associated with mutations in the SOD1 gene. Acta Neuropathologica, 135(1), 155-156. [More Information]
Trist, B., Davies, K., Cottam, V., Genoud, S., Ortega, R., Roudeau, S., Carmona, A., De Silva, K., Wasinger, V., Lewis, S., Ball, H., Halliday, G., Double, K., et al (2017). Amyotrophic lateral sclerosis-like superoxide dismutase 1 proteinopathy is associated with neuronal loss in Parkinson's disease brain. Acta Neuropathologica, 134(1), 113-127. [More Information]
Gotsbacher, M., Telfer, T., Witting, P., Double, K., Finkelstein, D., Codd, R. (2017). Analogues of desferrioxamine B designed to attenuate iron-mediated neurodegeneration: synthesis, characterisation and activity in the MPTP-mouse model of Parkinson's disease. Metallomics, 9(7), 852-864. [More Information]
Mathews, K., Allen, K., Boerrigter, D., Ball, H., Weickert, C., Double, K. (2017). Evidence for reduced neurogenesis in the aging human hippocampus despite stable stem cell markers. Aging Cell, 16(5), 1195-1199. [More Information]
Hare, D., Cardoso, B., Raven, E., Double, K., Finkelstein, D., Szymlek-Gay, E., Biggs, B. (2017). Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson's disease. NPJ Parkinson's Disease, 3(1), 1-5. [More Information]
Purves-Tyson, T., Owens, S., Rothmond, D., Halliday, G., Double, K., Stevens, J., McCrossin, T., Weickert, C. (2017). Putative presynaptic dopamine dysregulation in schizophrenia is supported by molecular evidence from post-mortem human midbrain. Translational Psychiatry, 7(1), 1-12. [More Information]
Double, K., Richards, L. (2017). Reducing the burden of neurological disease and mental illness. Medical Journal of Australia, 206(8), 341-342. [More Information]
Genoud, S., Roberts, B., Gunn, A., Halliday, G., Lewis, S., Ball, H., Hare, D., Double, K. (2017). Subcellular compartmentalisation of copper, iron, manganese, and zinc in the Parkinson's disease brain. Metallomics, 9(10), 1447-1455. [More Information]
Davies, K., Mercer, J., Chen, N., Double, K. (2016). Copper dyshomoeostasis in Parkinson's disease: Implications for pathogenesis and indications for novel therapeutics. Clinical Science, 130(8), 565-574. [More Information]
Weissleder, C., Fung, S., Wong, M., Barry, G., Double, K., Halliday, G., Webster, M., Weickert, C. (2016). Decline in proliferation and immature neuron markers in the human subependymal zone during aging: Relationship to EGF- and FGF-related transcripts. Frontiers in Aging Neuroscience, 8(NOV), 1-12. [More Information]
Hare, D., Double, K. (2016). Iron and dopamine: A toxic couple. Brain, 139(4), 1026-1035. [More Information]
Tan, B., Double, K., Burne, J., Diong, J. (2016). Tension-referenced measures of gastrocnemius slack length and stiffness in Parkinson's disease. Movement Disorders, 31(12), 1914-1918. [More Information]
Davies, K., Hare, D., Bohic, S., James, S., Billings, J., Finkelstein, D., Doble, P., Double, K. (2015). Comparative Study of Metal Quantification in Neurological Tissue Using Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry Imaging and X-ray Fluorescence Microscopy. Analytical Chemistry, 87(13), 6639-6645. [More Information]
Purves-Tyson, T., Boerrigter, D., Allen, K., Zavitsanou, K., Karl, T., Djunaidi, V., Double, K., Desai, R., Handelsman, D., Weickert, C. (2015). Testosterone attenuates and the selective estrogen receptor modulator, raloxifene, potentiates amphetamine-induced locomotion in male rats. Hormones and Behavior, 70, 73-84. [More Information]
Todd, G., Haberfield, M., Faulkner, P., Hayes, M., Wilcox, R., Rae, C., Bulathsinhala, T., Grunstein, R., Yee, B., Double, K. (2015). Upper limb function is normal in patients with restless legs syndrome (Willis-Ekbom Disease). Clinical Neurophysiology, 126(4), 736-742. [More Information]
Schroeder, R., Double, K., Gerber, J. (2015). Using Sepia melanin as a PD model to describe the binding characteristics of neuromelanin - A critical review. Journal of Chemical Neuroanatomy, 64-65, 20-32. [More Information]
Davies, K., Bohic, S., Carmona, A., Ortega, R., Cottam, V., Hare, D., Finberg, J., Reyes, S., Halliday, G., Mercer, J., Double, K. (2014). Copper pathology in vulnerable brain regions in Parkinson's disease. Neurobiology of Aging, 35(4), 858-866. [More Information]
Todd, G., Haberfield, M., Faulkner, P., Rae, C., Hayes, M., Wilcox, R., Taylor, J., Gandevia, S., Godau, J., Berg, D., Double, K., et al (2014). Hand function is impaired in healthy older adults at risk of Parkinson's disease. Journal of Neural Transmission, 121(11), 1377-1386. [More Information]
Hall, H., Reyes, S., Landeck, N., Bye, C., Leanza, G., Double, K., Thompson, L., Halliday, G., Kirik, D. (2014). Hippocampal Lewy pathology and cholinergic dysfunction are associated with dementia in Parkinson's disease. Brain, 137(9), 2493-2508. [More Information]
Purves-Tyson, T., Owens, S., Double, K., Desai, R., Handelsman, D., Weickert, C. (2014). Testosterone Induces Molecular Changes in Dopamine Signaling Pathway Molecules in the Adolescent Male Rat Nigrostriatal Pathway. PloS One, 9(3), 1-12. [More Information]
Dang, T., Dobson-Stone, C., Glaros, E., Kim, W., Hallupp, M., Bartley, L., Piguet, O., Hodges, J., Halliday, G., Double, K., et al (2013). Endogenous progesterone levels and frontotemporal dementia: Modulation of TDP-43 and Tau levels in vitro and treatment of the A315T TARDBP mouse model. Disease Models and Mechanisms, 6(5), 1198-1204. [More Information]
Davies, K., Hare, D., Cottam, V., Chen, N., Hilgers, L., Halliday, G., Mercer, J., Double, K. (2013). Localization of copper and copper transporters in the human brain. Metallomics, 5(1), 43-51. [More Information]
Reyes, S., Fu, Y., Double, K., Cottam, V., Thompson, L., Kirik, D., Paxinos, G., Watson, C., Cooper, H., Halliday, G. (2013). Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease. Neurobiology of Aging, 34(3), 873-886. [More Information]
Reyes, S., Cottam, V., Kirik, D., Double, K., Halliday, G. (2013). Variability in neuronal expression of dopamine receptors and transporters in the substantia nigra. Movement Disorders, 28(10), 1351-1359. [More Information]
Reyes, S., Fu, Y., Double, K., Thompson, L., Kirik, D., Paxinos, G., Halliday, G. (2012). GIRK2 expression in dopamine neurons of the substantia nigra and ventral tegmental area. Journal of Comparative Neurology, 520(12), 2591-2607. [More Information]
Chan, S., Dunlop, R., Rowe, A., Double, K., Rodgers, K. (2012). L-DOPA is incorporated into brain proteins of patients treated for Parkinson's disease, inducing toxicity in human neuroblastoma cells in vitro. Experimental Neurology, 238(1), 29-37. [More Information]
Double, K. (2012). Neuronal vulnerability in Parkinson's disease. Parkinsonism and Related Disorders, 18(Suppl 1), S52-S54. [More Information]
Purves-Tyson, T., Handelsman, D., Double, K., Owens, S., Bustamante, S., Weickert, C. (2012). Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra. BMC Neuroscience, 13(1), 1-12. [More Information]
Kurz, A., Double, K., Lastres-Becker, I., Tozzi, A., Tantucci, M., Bockhart, V., Bonin, M., Garcia-Arencibia, M., Nuber, S., Schlaudraff, F. (2010). A53T-alpha-synuclein overexpression impairs dopamine signaling and striatal synaptic plasticity in old mice. PloS One, 5(7), 1-15. [More Information]
Werry, E., Enjeti, S., Halliday, G., Sachdev, P., Double, K. (2010). Effect of age on proliferation-regulating factors in human adult neurogenic areas. Journal of Neurochemistry, 115(4), 956-964. [More Information]
Schofield, E., Halliday, G., Kwok, J., Loy, C., Double, K., Hodges, J. (2010). Low Serum Progranulin Predicts the Presence of Mutations: A Prospective Study. Journal of Alzheimer's Disease, 22(3), 981-984. [More Information]
Double, K., Todd, G., Duma, S. (2010). Pathophysiology of transcranial sonography signal changes in the human substantia nigra. International Review of Neurobiology, 90(C), 107-120. [More Information]
Double, K., Halliday, G., Dunkley, P., Dickson, P., Gerlach, M., Riederer, P. (2010). Pigmentation in the human brain and risk of Parkinson's disease. Annals of Neurology, 67(4), 553-554. [More Information]
Double, K., Reyes, S., Werry, E., Halliday, G. (2010). Selective cell death in neurodegeneration: why are some neurons spared in vulnerable regions? Progress in Neurobiology, 92(3), 316-329. [More Information]
Double, K., Rowe, D., Carew-Jones, F., Hayes, M., Chan, D., Blackie, J., Corbett, A., Joffe, R., Fung, V., Morris, J., et al (2009). Anti-melanin antibodies are increased in sera in Parkinson's disease. Experimental Neurology, 217, 297-301. [More Information]
Sutherland, G., Mellick, G., Newman, J., Double, K., Stevens, J., Lee, L., Rowe, D., Silburn, P., Halliday, G. (2008). Haplotype analysis of the IGF2-INS-TH gene cluster in Parkinson's disease. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 147B (4), 495-499. [More Information]
Bohic, S., Murphy, K., Paulus, W., Cloetens, P., Salome, M., Susini, J., Double, K. (2008). Intracellular chemical imaging of the developmental phases of human neuromelanin using synchrotron X-ray microspectroscopy. Analytical Chemistry, 80(24), 9557-9566. [More Information]
Gerlach, M., Riederer, P., Double, K. (2008). Neuromelanin-bound ferric iron as an experimental model of dopaminergic neurodegeneration in Parkinson's disease. Parkinsonism and Related Disorders, 14(Suppl. 2), S185-S188. [More Information]
Double, K., Dedov, V., Fedorow, H., Kettle, E., Halliday, G., Garner, B., Brunk, U. (2008). The comparative biology of neuromelanin and lipofuscin in the human brain. Cellular and Molecular Life Sciences, 65, 1669-1682. [More Information]
Gerlach, M., Deckert, J., Double, K., Koutsilieri, E. (2007). Journal of Neural Transmission, Supplementa: Preface. Journal of Neural Transmission, Supplementa, 27, V-VI.
Dedov, V., Griffiths, F., Garner, B., Halliday, G., Double, K. (2007). Lipid content determines aggregation of neuromelanin granules in vitro. Journal of Neural Transmission, Supplementa, 72, 35-38. [More Information]
Halliday, G., Fedorow, H., Rickert, C., Gerlach, M., Riederer, P., Double, K. (2006). Evidence for specific phases in the development of human neuromelanin. Journal of Neural Transmission, 113, 721-728. [More Information]
Fedorow, H., Halliday, G., Rickert, C., Gerlach, M., Riederer, P., Double, K. (2006). Evidence for specific phases in the development of human neuromelanin. Neurobiology of Aging, 27(3), 506-512. [More Information]
Fedorow, H., Pickford, R., Kettle, E., Cartwright, M., Halliday, G., Gerlach, M., Riederer, P., Garner, B., Double, K. (2006). Investigation of the lipid component of neuromelanin. Journal of Neural Transmission, 113, 735-739. [More Information]
Fedorow, H., Pickford, R., Hook, J., Double, K., Halliday, G., Gerlach, M., Riederer, P., Garner, B. (2005). Dolichol is the major lipid component of human substantia nigra neuromelanin. Journal of Neurochemistry, 92, 990-995. [More Information]
Fedorow, H., Tribl, F., Halliday, G., Gerlach, M., Riederer, P., Double, K. (2005). Neuromelanin in human dopamine neurons: Comparison with peripheral melanins and relevance to Parkinson's disease. Progress in Neurobiology, 75, 109-124. [More Information]
Halliday, G., Ophof, A., Broe, M., Jensen, P., Kettle, E., Fedorow, H., Cartwright, M., Griffiths, F., Shepherd, C., Double, K. (2005). Î±-Synuclein redistributes to neuromelanin lipid in the substantia nigra early in Parkinson's disease. Brain, 128, 2654-2664. [More Information]
Halliday, G., Double, K., Macdonald, V., Kril, J. (2003). Identifying severely atrophic cortical subregions in Alzheimer's disease. Neurobiology of Aging, 24(6), 797-806. [More Information]
Double, K., Rowe, D., Hayes, M., Chan, D., Blackie, J., Corbett, A., Joffe, R., Fung, V., Morris, J., Halliday, G. (2003). Identifying the Pattern of Olfactory Deficits in Parkinson Disease Using the Brief Smell Identification Test. JAMA Neurology, 60(4), 545-549. [More Information]
Double, K., Halliday, G., Henderson, J., Griffiths, F., Heinemann, T., Riederer, P., Gerlach, M. (2003). The dopamine receptor agonist lisuride attenuates iron-mediated dopaminergic neurodegeneration. Experimental Neurology, 184(1), 530-535. [More Information]

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2024

Zhu, J., Graziotto, M., Cottam, V., Hawtrey, T., Adair, L., Trist, B., Pham, T., Rouaen, J., Ohno, C., Heisler, M., Double, K., New, E., et al (2024). Near-Infrared Ratiometric Fluorescent Probe for Detecting Endogenous Cu2+ in the Brain. ACS Sensors, 9(6), 2858-2868. [More Information]

2023

Penning, L., Berenguer, M., Czlonkowska, A., Double, K., Dusek, P., Espinós, C., Lutsenko, S., Medici, V., Papenthin, W., Stremmel, W., et al (2023). A Century of Progress on Wilson Disease and the Enduring Challenges of Genetics, Diagnosis, and Treatment. Biomedicines, 11(2). [More Information]
Todd, G., Rae, C., Taylor, J., Rogasch, N., Butler, J., Hayes, M., Wilcox, R., Gandevia, S., Aoun, K., Esterman, A., Lewis, S., Matar, E., Double, K., et al (2023). Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity. Journal of Neuroscience Research, 101(2), 263-277. [More Information]
Diong, J., Bero, L., Double, K., Ong, Y. (2023). Responsible research practices could be more strongly endorsed by Australian university codes of research conduct. Research Integrity and Peer Review.

2022

Foley, P., Hare, D., Double, K. (2022). A brief history of brain iron accumulation in Parkinson disease and related disorders. Journal of Neural Transmission, 129(2023-06-05 00:00:00), 505-520. [More Information]
Trist, B., Genoud, S., Roudeau, S., Rookyard, A., Abdeen, A., Cottam, V., Hare, D., White, M., Altvater, J., Fifita, J., Cordwell, S., Halliday, G., Double, K., et al (2022). Altered SOD1 maturation and post-translational modification in amyotrophic lateral sclerosis spinal cord. Brain, 145(9), 3108-3130. [More Information]
Trist, B., Fifita, J., Hogan, A., Grima, N., Smith, B., Troakes, C., Vance, C., Shaw, C., Al-Sarraj, S., Blair, I., Double, K. (2022). Co-deposition of SOD1, TDP-43 and p62 proteinopathies in ALS: evidence for multifaceted pathways underlying neurodegeneration. Acta Neuropathologica Communications, 10(1). [More Information]
Abdeen, A., Trist, B., Double, K. (2022). Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis. NPJ Parkinson's Disease, 8(1). [More Information]
John, A., Singh, A., Nguyen Do, T., Eidels, A., Nalivaiko, E., Gavgani, A., Brown, S., Bennett, M., Lal, S., Simpson, A., Double, K., Kleitman, S., et al (2022). Unravelling the Physiological Correlates of Mental Workload Variations in Tracking and Collision Prediction Tasks. IEEE Transactions on Neural Systems and Rehabilitation Engineering, 30, 770-781. [More Information]

show 2 more

2021

Aoun, K., Double, K., Pearson-Dennett, V., Yilmaz, R., Berg, D., Todd, G. (2021). Measurement of the adult human midbrain with transcranial ultrasound. PloS One, 16, e0247920. [More Information]
Roudeau, S., Trist, B., Carmona, A., Davies, K., Halliday, G., Rufin, Y., Claverol, S., Van Malderen, S., Falkenberg, G., Double, K., et al (2021). Native Separation and Metallation Analysis of SOD1 Protein from the Human Central Nervous System: A Methodological Workflow. Analytical Chemistry, 93(32), 11108-11115. [More Information]
Trist, B., Hilton, J., Hare, D., Crouch, P., Double, K. (2021). Superoxide Dismutase 1 in Health and Disease: How a Frontline Antioxidant Becomes Neurotoxic. Angewandte Chemie - International Edition, 60(17), 9215-9246. [More Information]

2020

Genoud, S., Senior, A., Hare, D., Double, K. (2020). Meta-Analysis of Copper and Iron in Parkinson's Disease Brain and Biofluids. Movement Disorders, 35(4), 662-671. [More Information]
Genoud, S., Jones, M., Trist, B., Deng, J., Chen, S., Hare, D., Double, K. (2020). Simultaneous structural and elemental nano-imaging of human brain tissue. Chemical Science, 11(33), 8919-8927. [More Information]

2019

Shehadeh, J., Double, K., Murphy, K., Bobrovskaya, L., Reyes, S., Dunkley, P., Halliday, G., Dickson, P. (2019). Expression of tyrosine hydroxylase isoforms and phosphorylation at serine 40 in the human nigrostriatal system in Parkinson's disease. Neurobiology of Disease, 130, 1-8. [More Information]
Virachit, S., Mathews, K., Cottam, V., Werry, E., Galli, E., Rappou, E., Lindholm, P., Saarma, M., Halliday, G., Shannon Weickert, C., Double, K. (2019). Levels of glial cell line-derived neurotrophic factor are decreased, but fibroblast growth factor 2 and cerebral dopamine neurotrophic factor are increased in the hippocampus in Parkinson's disease. Brain Pathology, 29(6), 813-825. [More Information]
Trist, B., Hare, D., Double, K. (2019). Oxidative stress in the aging substantia nigra and the etiology of Parkinson's disease. Aging Cell, 18(6), 1-23. [More Information]
Weissleder, C., Barry, G., Fung, S., Wong, M., Double, K., Webster, M., Weickert, C. (2019). Reduction in IGF1 mRNA in the Human Subependymal Zone During Aging. Aging and Disease, 10(1), 197-204. [More Information]

show 1 more

2018

Trist, B., Hare, D., Double, K. (2018). A Proposed Mechanism for Neurodegeneration in Movement Disorders Characterized by Metal Dyshomeostasis and Oxidative Stress. Cell Chemical Biology, 25(7), 807-816. [More Information]
Trist, B., Fifita, J., Freckleton, S., Hare, D., Lewis, S., Halliday, G., Blair, I., Double, K. (2018). Accumulation of dysfunctional SOD1 protein in Parkinson's disease is not associated with mutations in the SOD1 gene. Acta Neuropathologica, 135(1), 155-156. [More Information]

2017

Trist, B., Davies, K., Cottam, V., Genoud, S., Ortega, R., Roudeau, S., Carmona, A., De Silva, K., Wasinger, V., Lewis, S., Ball, H., Halliday, G., Double, K., et al (2017). Amyotrophic lateral sclerosis-like superoxide dismutase 1 proteinopathy is associated with neuronal loss in Parkinson's disease brain. Acta Neuropathologica, 134(1), 113-127. [More Information]
Gotsbacher, M., Telfer, T., Witting, P., Double, K., Finkelstein, D., Codd, R. (2017). Analogues of desferrioxamine B designed to attenuate iron-mediated neurodegeneration: synthesis, characterisation and activity in the MPTP-mouse model of Parkinson's disease. Metallomics, 9(7), 852-864. [More Information]
Mathews, K., Allen, K., Boerrigter, D., Ball, H., Weickert, C., Double, K. (2017). Evidence for reduced neurogenesis in the aging human hippocampus despite stable stem cell markers. Aging Cell, 16(5), 1195-1199. [More Information]
Hare, D., Cardoso, B., Raven, E., Double, K., Finkelstein, D., Szymlek-Gay, E., Biggs, B. (2017). Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson's disease. NPJ Parkinson's Disease, 3(1), 1-5. [More Information]
Purves-Tyson, T., Owens, S., Rothmond, D., Halliday, G., Double, K., Stevens, J., McCrossin, T., Weickert, C. (2017). Putative presynaptic dopamine dysregulation in schizophrenia is supported by molecular evidence from post-mortem human midbrain. Translational Psychiatry, 7(1), 1-12. [More Information]
Double, K., Richards, L. (2017). Reducing the burden of neurological disease and mental illness. Medical Journal of Australia, 206(8), 341-342. [More Information]
Genoud, S., Roberts, B., Gunn, A., Halliday, G., Lewis, S., Ball, H., Hare, D., Double, K. (2017). Subcellular compartmentalisation of copper, iron, manganese, and zinc in the Parkinson's disease brain. Metallomics, 9(10), 1447-1455. [More Information]

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2016

Davies, K., Mercer, J., Chen, N., Double, K. (2016). Copper dyshomoeostasis in Parkinson's disease: Implications for pathogenesis and indications for novel therapeutics. Clinical Science, 130(8), 565-574. [More Information]
Weissleder, C., Fung, S., Wong, M., Barry, G., Double, K., Halliday, G., Webster, M., Weickert, C. (2016). Decline in proliferation and immature neuron markers in the human subependymal zone during aging: Relationship to EGF- and FGF-related transcripts. Frontiers in Aging Neuroscience, 8(NOV), 1-12. [More Information]
Hare, D., Double, K. (2016). Iron and dopamine: A toxic couple. Brain, 139(4), 1026-1035. [More Information]
Tan, B., Double, K., Burne, J., Diong, J. (2016). Tension-referenced measures of gastrocnemius slack length and stiffness in Parkinson's disease. Movement Disorders, 31(12), 1914-1918. [More Information]

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2015

Davies, K., Hare, D., Bohic, S., James, S., Billings, J., Finkelstein, D., Doble, P., Double, K. (2015). Comparative Study of Metal Quantification in Neurological Tissue Using Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry Imaging and X-ray Fluorescence Microscopy. Analytical Chemistry, 87(13), 6639-6645. [More Information]
Purves-Tyson, T., Boerrigter, D., Allen, K., Zavitsanou, K., Karl, T., Djunaidi, V., Double, K., Desai, R., Handelsman, D., Weickert, C. (2015). Testosterone attenuates and the selective estrogen receptor modulator, raloxifene, potentiates amphetamine-induced locomotion in male rats. Hormones and Behavior, 70, 73-84. [More Information]
Todd, G., Haberfield, M., Faulkner, P., Hayes, M., Wilcox, R., Rae, C., Bulathsinhala, T., Grunstein, R., Yee, B., Double, K. (2015). Upper limb function is normal in patients with restless legs syndrome (Willis-Ekbom Disease). Clinical Neurophysiology, 126(4), 736-742. [More Information]
Schroeder, R., Double, K., Gerber, J. (2015). Using Sepia melanin as a PD model to describe the binding characteristics of neuromelanin - A critical review. Journal of Chemical Neuroanatomy, 64-65, 20-32. [More Information]

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2014

Davies, K., Bohic, S., Carmona, A., Ortega, R., Cottam, V., Hare, D., Finberg, J., Reyes, S., Halliday, G., Mercer, J., Double, K. (2014). Copper pathology in vulnerable brain regions in Parkinson's disease. Neurobiology of Aging, 35(4), 858-866. [More Information]
Todd, G., Haberfield, M., Faulkner, P., Rae, C., Hayes, M., Wilcox, R., Taylor, J., Gandevia, S., Godau, J., Berg, D., Double, K., et al (2014). Hand function is impaired in healthy older adults at risk of Parkinson's disease. Journal of Neural Transmission, 121(11), 1377-1386. [More Information]
Hall, H., Reyes, S., Landeck, N., Bye, C., Leanza, G., Double, K., Thompson, L., Halliday, G., Kirik, D. (2014). Hippocampal Lewy pathology and cholinergic dysfunction are associated with dementia in Parkinson's disease. Brain, 137(9), 2493-2508. [More Information]
Purves-Tyson, T., Owens, S., Double, K., Desai, R., Handelsman, D., Weickert, C. (2014). Testosterone Induces Molecular Changes in Dopamine Signaling Pathway Molecules in the Adolescent Male Rat Nigrostriatal Pathway. PloS One, 9(3), 1-12. [More Information]

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2013

Dickson, P., Shehadeh, J., Double, K., Bobrovskaya, L., Reyes, S., Dunkley, P., Halliday, G. (2013). Analysis of Tyrosine Hydroxylase Isoforms and Phosphorylation in Parkinson's Disease. In Lee E. Eiden (Eds.), Catecholamine Research in the 21st Century: Abstracts and Graphical Abstracts, 10th International Catecholamine Symposium, 2012, (pp. 15-15). London: Elsevier. [More Information]
Dang, T., Dobson-Stone, C., Glaros, E., Kim, W., Hallupp, M., Bartley, L., Piguet, O., Hodges, J., Halliday, G., Double, K., et al (2013). Endogenous progesterone levels and frontotemporal dementia: Modulation of TDP-43 and Tau levels in vitro and treatment of the A315T TARDBP mouse model. Disease Models and Mechanisms, 6(5), 1198-1204. [More Information]
Davies, K., Hare, D., Cottam, V., Chen, N., Hilgers, L., Halliday, G., Mercer, J., Double, K. (2013). Localization of copper and copper transporters in the human brain. Metallomics, 5(1), 43-51. [More Information]
Double, K., Finberg, J. (2013). Parkinson's Disease. In Donald W. Pfaff (Eds.), Neuroscience in the 21st Century: From Basic to Clinical, (pp. 2903-2921). New York: Springer.
Reyes, S., Fu, Y., Double, K., Cottam, V., Thompson, L., Kirik, D., Paxinos, G., Watson, C., Cooper, H., Halliday, G. (2013). Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease. Neurobiology of Aging, 34(3), 873-886. [More Information]
Reyes, S., Cottam, V., Kirik, D., Double, K., Halliday, G. (2013). Variability in neuronal expression of dopamine receptors and transporters in the substantia nigra. Movement Disorders, 28(10), 1351-1359. [More Information]

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2012

Reyes, S., Fu, Y., Double, K., Thompson, L., Kirik, D., Paxinos, G., Halliday, G. (2012). GIRK2 expression in dopamine neurons of the substantia nigra and ventral tegmental area. Journal of Comparative Neurology, 520(12), 2591-2607. [More Information]
Chan, S., Dunlop, R., Rowe, A., Double, K., Rodgers, K. (2012). L-DOPA is incorporated into brain proteins of patients treated for Parkinson's disease, inducing toxicity in human neuroblastoma cells in vitro. Experimental Neurology, 238(1), 29-37. [More Information]
Double, K. (2012). Neuronal vulnerability in Parkinson's disease. Parkinsonism and Related Disorders, 18(Suppl 1), S52-S54. [More Information]
Halliday, G., Reyes, S., Double, K. (2012). Substantia Nigra, Ventral Tegmental Area, and Retrorubral Fields. In Juergen K. Mai and George Paxinos (Eds.), The Human Nervous System, (pp. 439-455). London: Academic Press. [More Information]
Purves-Tyson, T., Handelsman, D., Double, K., Owens, S., Bustamante, S., Weickert, C. (2012). Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra. BMC Neuroscience, 13(1), 1-12. [More Information]

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2011

Double, K., Maruyama, W., Naoi, M., Gerlach, M., Riederer, P. (2011). Biological Role of Neuromelanin in the Human Brain and Its Importance in Parkinson's Disease. In Jan Borovansky, Patrick A. Riley (Eds.), Melanins and Melanosomes: Biosynthesis, Biogenesis, Physiological, and Pathological Functions, (pp. 225-246). Weinheim, Germany: Wiley - V C H Verlag GmbH & Co. KGaA.

2010

Kurz, A., Double, K., Lastres-Becker, I., Tozzi, A., Tantucci, M., Bockhart, V., Bonin, M., Garcia-Arencibia, M., Nuber, S., Schlaudraff, F. (2010). A53T-alpha-synuclein overexpression impairs dopamine signaling and striatal synaptic plasticity in old mice. PloS One, 5(7), 1-15. [More Information]
Werry, E., Enjeti, S., Halliday, G., Sachdev, P., Double, K. (2010). Effect of age on proliferation-regulating factors in human adult neurogenic areas. Journal of Neurochemistry, 115(4), 956-964. [More Information]
Schofield, E., Halliday, G., Kwok, J., Loy, C., Double, K., Hodges, J. (2010). Low Serum Progranulin Predicts the Presence of Mutations: A Prospective Study. Journal of Alzheimer's Disease, 22(3), 981-984. [More Information]
Double, K., Todd, G., Duma, S. (2010). Pathophysiology of transcranial sonography signal changes in the human substantia nigra. International Review of Neurobiology, 90(C), 107-120. [More Information]
Double, K., Halliday, G., Dunkley, P., Dickson, P., Gerlach, M., Riederer, P. (2010). Pigmentation in the human brain and risk of Parkinson's disease. Annals of Neurology, 67(4), 553-554. [More Information]
Double, K., Reyes, S., Werry, E., Halliday, G. (2010). Selective cell death in neurodegeneration: why are some neurons spared in vulnerable regions? Progress in Neurobiology, 92(3), 316-329. [More Information]

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2009

Double, K., Rowe, D., Carew-Jones, F., Hayes, M., Chan, D., Blackie, J., Corbett, A., Joffe, R., Fung, V., Morris, J., et al (2009). Anti-melanin antibodies are increased in sera in Parkinson's disease. Experimental Neurology, 217, 297-301. [More Information]

2008

Sutherland, G., Mellick, G., Newman, J., Double, K., Stevens, J., Lee, L., Rowe, D., Silburn, P., Halliday, G. (2008). Haplotype analysis of the IGF2-INS-TH gene cluster in Parkinson's disease. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 147B (4), 495-499. [More Information]
Bohic, S., Murphy, K., Paulus, W., Cloetens, P., Salome, M., Susini, J., Double, K. (2008). Intracellular chemical imaging of the developmental phases of human neuromelanin using synchrotron X-ray microspectroscopy. Analytical Chemistry, 80(24), 9557-9566. [More Information]
Gerlach, M., Riederer, P., Double, K. (2008). Neuromelanin-bound ferric iron as an experimental model of dopaminergic neurodegeneration in Parkinson's disease. Parkinsonism and Related Disorders, 14(Suppl. 2), S185-S188. [More Information]
Double, K., Dedov, V., Fedorow, H., Kettle, E., Halliday, G., Garner, B., Brunk, U. (2008). The comparative biology of neuromelanin and lipofuscin in the human brain. Cellular and Molecular Life Sciences, 65, 1669-1682. [More Information]

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2007

Gerlach, M., Deckert, J., Double, K., Koutsilieri, E. (2007). Journal of Neural Transmission, Supplementa: Preface. Journal of Neural Transmission, Supplementa, 27, V-VI.
Dedov, V., Griffiths, F., Garner, B., Halliday, G., Double, K. (2007). Lipid content determines aggregation of neuromelanin granules in vitro. Journal of Neural Transmission, Supplementa, 72, 35-38. [More Information]
Gerlach, M., Deckert, J., Double, K., Koutsilieri, E. (2007). Neuropyschiatric disorders: an integrative approach. J. Neural Trans. Suppl 72. New York: Springer.

2006

Halliday, G., Fedorow, H., Rickert, C., Gerlach, M., Riederer, P., Double, K. (2006). Evidence for specific phases in the development of human neuromelanin. Journal of Neural Transmission, 113, 721-728. [More Information]
Fedorow, H., Halliday, G., Rickert, C., Gerlach, M., Riederer, P., Double, K. (2006). Evidence for specific phases in the development of human neuromelanin. Neurobiology of Aging, 27(3), 506-512. [More Information]
Fedorow, H., Pickford, R., Kettle, E., Cartwright, M., Halliday, G., Gerlach, M., Riederer, P., Garner, B., Double, K. (2006). Investigation of the lipid component of neuromelanin. Journal of Neural Transmission, 113, 735-739. [More Information]

2005

Fedorow, H., Pickford, R., Hook, J., Double, K., Halliday, G., Gerlach, M., Riederer, P., Garner, B. (2005). Dolichol is the major lipid component of human substantia nigra neuromelanin. Journal of Neurochemistry, 92, 990-995. [More Information]
Fedorow, H., Tribl, F., Halliday, G., Gerlach, M., Riederer, P., Double, K. (2005). Neuromelanin in human dopamine neurons: Comparison with peripheral melanins and relevance to Parkinson's disease. Progress in Neurobiology, 75, 109-124. [More Information]
Halliday, G., Ophof, A., Broe, M., Jensen, P., Kettle, E., Fedorow, H., Cartwright, M., Griffiths, F., Shepherd, C., Double, K. (2005). Î±-Synuclein redistributes to neuromelanin lipid in the substantia nigra early in Parkinson's disease. Brain, 128, 2654-2664. [More Information]

2003

Halliday, G., Double, K., Macdonald, V., Kril, J. (2003). Identifying severely atrophic cortical subregions in Alzheimer's disease. Neurobiology of Aging, 24(6), 797-806. [More Information]
Double, K., Rowe, D., Hayes, M., Chan, D., Blackie, J., Corbett, A., Joffe, R., Fung, V., Morris, J., Halliday, G. (2003). Identifying the Pattern of Olfactory Deficits in Parkinson Disease Using the Brief Smell Identification Test. JAMA Neurology, 60(4), 545-549. [More Information]
Double, K., Halliday, G., Henderson, J., Griffiths, F., Heinemann, T., Riederer, P., Gerlach, M. (2003). The dopamine receptor agonist lisuride attenuates iron-mediated dopaminergic neurodegeneration. Experimental Neurology, 184(1), 530-535. [More Information]

Selected Grants

2024

Partnering with industry to develop ultrasensitive SOD1 assays for improved diagnosis and understanding of ALS, Trist B, Double K, Motor Neurone Disease Research Institute of Australia/Innovator Grant

2023

Rewarding Research 2024, Double K, Faculty of Medicine and Health/FMH Rewarding Research Success

2022

The first tool to quantify brain copper during life, Double K, New E, Meikle S, National Health and Medical Research Council (NHMRC)/Ideas Grant

2019

Superoxide dismutase one dysfunction: a novel pathogenic mechanism in Parkinson disease, Double K, Hare D, Codd R, National Health and Medical Research Council (NHMRC)/Ideas Grant
Does dopamine cell death result from a novel proteinopathy in Parkinsons Disease brain, Double K, Cordwell S, Codd R, Trist B, Michael J Fox Foundation for Parkinsons Research/Research Support
Perpetual account for travel grants for A/ Prof. Kay Double, Double K, Genoud S, Australian Synchrotron/Funding Application for Interstate User Groups
Validating molecular pathways of SOD1 toxicity in human ALS, Double K, Trist B, Cordwell S, Motor Neurone Disease Research Institute of Australia/Motor Neurone Disease Research Grants

2018

A Set-up for Multi-analyte Spatial Profiling Platform in 3D Neuroscience, Double K, Fu Y, Halliday G, National Health and Medical Research Council (NHMRC)/Equipment Grant

2017

Why does toxic Superoxide dismutase 1 aggregate in degenerating regions of the Parkinson's disease brain?, Double K, Hare D, Parkinsons New South Wales Incorporated/Research Grants

2016

Mechanism and toxicity of superoxide dismutase-one aggregation in Parkinson's disease, Double K, Hare D, Parkinsons New South Wales Incorporated/Research Grants

2015

Superoxide dismutase one: a novel protein aggregate in Parkinson's disease, Double K, Hare D, Parkinsons New South Wales Incorporated/Research Grants

2014

Potential of ionophore therapy for neuroprotection in Parkinsons disease, Double K, Finkelstein D, Parkinsons New South Wales Incorporated/Research Grants

2013

Agents targeting iron in the brain in Parkinsons disease, Codd R, Double K, Liddell J, Witting P, National Health and Medical Research Council (NHMRC)/Project Grants
Restoring brain copper in a murine model of copper deficiency, Double K, Finkelstein D, University of Sydney/Internal Research Grant Allocations
Does rigidity in Parkinson's disease change the passive mechanical properties of muscle?, Diong J, Double K, University of Sydney/Internal Research Grant Allocations

2012

A role for the Parkinson proteins Î±-synuclein and LRRK2 in altered brain cell birth in a Parkinson's disease, Double K, Parkinsons New South Wales Incorporated/Research Support

2011

Human tyrosine hydroxylase isoforms and susceptibility of dopaminergic neurons to degeneration in Parkinsons's disease, Dickson P, Dunkley P, Double K, National Health and Medical Research Council (NHMRC)/Project Grants
Molecular mechanism of testosterone action on midbrain dopamine neuron differentiation, Double K, Shannon Weickert C, National Health and Medical Research Council (NHMRC)/Project Grants

2010

Copper pathways are altered in Parkinson's disease: Implications for cell vulnerability, Double K, Finkelstein D, Mercer J, National Health and Medical Research Council (NHMRC)/Project Grants

2009

Synchrotron microprobe analysis of copper changes in murine models of neurodegenerative disease, Double K, International Sciences Linkages Programme/French-Australian Science and Technology Programme

Faculty of Medicine and Health

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Professor Kay Double

Selected publications

Publications

Selected Grants

2024

2023

2022

2019

2018

2017

2016

2015

2014

2013

2012

2011

2010

2009

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