Florey Department of Neuroscience and Mental Health

Masters studied medicine at the University of Western Australia. He opted for an extra year of pre-medical studies in 1967, which he spent doing neuropathology research, and graduated M.B. B.S. in 1970. He completed his M.D. in medical neuropathology in 1977 after research fellowships at the University of Western Australia and Massachusetts General Hospital. After positions as visiting scientist at the National Institute of Neurological Disorders and Stroke and Humboldt fellow at Heidelberg University, he returned to Western Australia and Royal Perth Hospital in 1981 as a clinician-scientist. In 1989 he relocated to the University of Melbourne where he spent the rest of his career as consultant pathologist and professor of pathology, becoming a laureate professor in 2002 and serving for six years as associate dean of research at the medical and dental school.

Masters and his erstwhile colleague from Heidelberg Konrad Beyreuther were the first to characterize the amyloid protein that forms the cerebral plaques observed in Alzheimer's Disease (AD) and Down's Syndrome (DS, also known as trisomy 21). Known as amyloid-beta (Aβ), this peptide is derived from amyloid precursor protein (APP), which was subsequently mapped to the region of chromosome 21 that is altered in DS. The notion that Aβ causes AD, called the amyloid hypothesis, gained force from genetic studies that traced familial forms of the disease to variations in the APP gene. Masters became a prominent proponent of the amyloid hypothesis, developing strategies for anti-Alzheimer's treatments that suppress the beta-secretase and gamma-secretase enzymes that cleave APP to form Aβ or modify the interactions between metal ions and Aβ that are important for its toxic effects. Despite two decades of intensive research, however, these approaches have not yielded useful drugs.