The onset of Alzheimer’s disease could be delayed by a molecule that occurs naturally in humans, research suggests.
The study in mice showed that the “housekeeping” molecule put the brakes on a runaway process in the brain that leads to the most common form of dementia.
The substance works by slowing the accumulation of sticky clumps of protein in the brain, which typically appear years before symptoms such as memory loss become apparent in patients.
Although the molecule tested would be difficult to convert into a drug for use in humans, the scientists said, the findings prove that the cycle that leads to Alzheimer’s devastating impact on memory and personality can be interrupted.
Samuel Cohen, who led the study at the University of Cambridge, said: “The big advantage is that we haven’t just come up with a drug and not really understood what it is doing. We’ve come up with a general strategy that could work.”
In the earliest stages of Alzheimer’s – long before any outward signs of the disease – proteins in the brain, called amyloid betas start folding into the wrong shape, causing them to stick together in clumps. The clumps slowly grow into long hair-like threads, or fibrils, spreading across the brain. Although the brain has built-in mechanisms to eliminate faulty proteins, this cleanup process quickly falls behind because the fibrils themselves act as a “catalyst” for the formation of further clumps. “Initially the process is really slow, but it becomes a runaway chain reaction,” said Cohen.
Dementia affects around 820,000 people in the UK. Scientists estimate that delaying the onset of Alzheimer’s by five years would halve the number of people who die with the disease.
The latest study, published on Monday in the journal Nature Structural & Molecular Biology, showed that a human molecule, called Brichos, sticks to the amyloid fibrils and, by coating their exterior, stops them from accelerating the formation of more clumps.
“It doesn’t stop the initial formation, but it stops it becoming a chain reaction,” said Cohen.
The scientists tested the molecule in mice that had been given injections of amyloid proteins into the brain to mimic the biology of Alzheimer’s. Normally this reduces the level of electrical activity called “gamma waves” in the brain – an indicator of the toxic effect of the clumpy protein. However, when mice were injected with amyloid proteins together with Brichos, their brains appeared to be protected and their gamma wave activity was indistinguishable from that in healthy control mice.
Brichos is unlikely to be suitable as a drug because it would be absorbed by the body before having the chance to work in the brain. “A good tactic now is to search for other molecules that have this same highly targeted effect and to see if these can be used as the starting point for developing a future therapy,” said Cohen.
Dr Laura Phipps of Alzheimer’s Research UK, said: “This detailed study has revealed a potential way to prevent the build-up of amyloid, and highlights a possible new avenue for research into new treatments for Alzheimer’s disease. Researchers are working hard to identify the molecular process that are most toxic to nerve cells in Alzheimer’s and this technically challenging study has revealed clues to how to block one important chain of events in the disease.”
http://www.theguardian.com/science/2015/feb/16/alzheimers-research-molecule-delay-onset-dementia-found
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