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Alzheimer's Unlocked: New Keys to a Cure

from New Scientist

... For the past two decades, Alzheimer's research has been dominated by the "amyloid cascade hypothesis": the idea that it is the plaques themselves that lead to the cognitive problems of Alzheimer's. They are aggregations of a protein called amyloid beta, which forms naturally in the brain, but whose production somehow goes into overdrive during Alzheimer's disease. The proteins clump together to form plaques, which are toxic to neurons, eventually killing them, or so the theory goes.

... The excitement has faded fast. So far, at least, none of the treatments derived from the amyloid hypothesis has ever resulted in significant clinical improvement in clinical trials. "It has been a problem for people working on [the amyloid plaque theory] for 20 years--the drugs that have come out of it have all failed at stage II or III of clinical trials," says Susanne Sorensen, head of research at the UK's Alzheimer's Society. Sorensen has never seen a trial that reported people getting better.

Take b-mab, for example. This drug was developed to clear amyloid plaques from the brain, but results released in 2008 showed that it had no significant effect on the rate of cognitive decline (Neurology, vol 73, p 2061). That raised a question. Was b-mab failing to clear the plaques, or were the plaques themselves not the problem?

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