There is now compelling evidence that Aβ is the cause of Alzheimer’s disease. Initially formulated as a hypothesis in the 1970’s when characterization of the amyloid deposits in AD started, after successful cloning of the APP gene in 1987, the evidence quickly amassed that Aβ/APP was at the core of AD, and that tau and neurofibrillary tangles were downstream of Aβ.

Over the past decade, this Aβ hypothesis has matured to a point where a comprehensive Aβ theory has emerged, in which oligomeric species of Aβ are responsible for causing synaptic degeneration in the AD brain. As with all scientific theories, one can only test their validity by challenging the concept. For the Aβ theory of AD, this means that tests of Aβ damage in the AD brain (for example, as assessed by PET-amyloid imaging and Aβ quantitation in CSF) must be incorporated into therapeutic strategies which target the Aβ pathway.

Our current goal is to identify and characterize the precise Aβ-related targets (the Aβ production pathways, the Aβ oligomer itself, the Aβ clearance pathways) and then develop appropriate therapeutic strategies. As an essential prerequisite, it is now clear that intervention must occur at the earliest possible stage of Aβ accumulation. Using longitudinal cohort analyses such as the Australian Imaging, Biomarker and Lifestyle (AIBL) study, the natural history of AD is becoming clearer, with the visualization of Aβ accumulation commencing decades before the onset of cerebral atrophy and cognitive decline. These insights will enable definitive tests of the Aβ theory to be conducted in the near future.

Analyses of this type in Alzheimer’s disease is having a major impact in related neurodegenerative conditions such as Parkinson’s disease and Creutzfeldt-Jakob disease.

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Colin Masters graduated in medicine at the University of Western Australia, and began his research career studying ‘slow virus diseases’ of the brain, such as prion diseases, which led him to study amyloid deposits in Alzheimer’s patients. With his collaborators, he purified, identified amyloid proteins, and sequenced the gene.

In 2000, he turned his focus to the environmental and genetic contributors to Alzheimer’s. His shift coincided with industry collaborations geared towards developing therapies for the disease, and the co-founding of a small biotech company called Prana Biotechnology, but he still spends most of his time doing research.

Forthcoming talks:

May    15 ^th     Dr Angus Johnston, ARC Future Fellow, NanoMaterials for Biology Group

June     19^th      A/Prof Mike Lawrence, Structural Biology, WEHI

July      17^th      Prof Franz Grieser, Sonochemistry, Particulate Fluids Processing Centre

 We are pleased to acknowledge the support by CSL, GTAC, and the Faculty of Science, Melbourne University, for the ANZAAS Melbourne science talks series

 Further Info:         David Vaux       Ph: 9345 2941               E-mail:  davidlaurencevaux@gmail.com