S.M. Wilson, J. Patel, S. Dealler, R. Rosedale, C.J. Stanley

Any major improvements to lifespan are likely to increase the prevalence of age related diseases such as Alzheimer's Disease (AD). AD is almost exclusively a disease in those aged 65 or older and the prevalence increases with age. It is predicted that even with today's ageing population the prevalence of AD will increase significantly. In AD the brain has a number of changes that can be linked to pathology including aggregates of tau and beta amyloid proteins. The amyloid aggregates, particularly the smaller oligomeric aggregates, have been linked to toxicity and have been implicated in neuronal death. It is important to study these oligomeric aggregates in order to find compounds, potential drugs, which can both prevent aggregation and perhaps dissociate toxic aggregates that have already formed. We have developed a ligand, Seprion, that can bind to the aggregates of a class of protein aggregation diseases including AD, Parkinson's Disease, Huntingdon's Disease and prion diseases including vCJD in man, BSE in cattle and scrapie in sheep. The ligand has been built into tests for BSE in cattle brain (these tests have received USDA and EU-approval), vCJD in human blood and has been used successfully to differentiate AD brain from normal brain in a small blind panel of samples. Recently we have built this ligand into a drug screening assay for compounds that affect beta amyloid aggregation. The most effective compounds that we have identified by this screen have been tested in a mouse model of human AD and have demonstrated a reduction in detergent soluble aggregates in the brain and a reduction of aggregates as observed by immunohistochemical analysis of the brain.

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