Scientists ID a Molecular Trigger for Alzheimer’s Disease

Researchers have pinpointed a catalytic trigger for the onset of Alzheimer’s disease – when the fundamental structure of a protein molecule changes to cause a chain reaction that leads to the death of neurons in the brain. For the first time, scientists at Cambridge’s Department of Chemistry have been able to map in detail the pathway that generates “aberrant” forms of proteins that are at the root of neurodegenerative conditions such as Alzheimer’s. They believe the breakthrough is a vital step closer to increased capabilities for earlier diagnosis of neurological disorders such as Alzheimer’s and Parkinson’s, and opens up possibilities for a new generation of targeted drugs, as scientists say they have uncovered the earliest stages of the development of Alzheimer’s that drugs could possibly target. The study, published online on May 20, 2013 in PNAS, is a milestone in the long-term research established in Cambridge by Professor Christopher Dobson and his colleagues, following the realization by Dr. Dobson of the underlying nature of protein ‘misfolding’ and its connection with disease over 15 years ago. The research is likely to have a central role to play in diagnostic and drug development for dementia-related diseases, which are increasingly prevalent and damaging as populations live longer. “There are no disease-modifying therapies for Alzheimer’s and dementia at the moment, only limited treatment for symptoms. We have to solve what happens at the molecular level before we can progress and have real impact,” said Dr Tuomas Knowles, lead author of the study and long-time collaborator of Professor Dobson’s. “We’ve now established the pathway that shows how the toxic species that cause cell death, the oligomers, are formed.
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