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Black hat in Alzheimer's, white hat in multiple sclerosis?

Possibly no protein has a worse reputation than beta-amyloid, or A-beta, a protein snippet (or "peptide") that collects in the brain to become the chief component of clumps called amyloid plaques. Plenty of Alzheimer's disease researchers believe these plaques are not only a hallmark but in fact a major cause of the condition.

There's every reason to believe that A-beta is neurotoxic. Yet, in a study just published in Science Translational Medicine, noted multiple-sclerosis expert Larry Steinman, MD, and his colleagues have identified a potentially heroic role for the peptide. When the Stanford investigators injected A-beta into the bellies of mice exposed to a regimen that is known to induce an MS-like condition, A-beta variously reduced, reversed or prevented the paralysis that's an almost inevitable feature of the mouse version of MS.

When Steinman's group observed that the experimental mice that got A-beta injections did much better, rather than much worse, than those who'd received blank injections, at first they didn't believe it.

Many painstaking iterations later, they concluded that A-beta, administered on the far side of the blood-brain barrier, dials down the activity of immune cells that would otherwise invade the mice's brains and attack the myelin sheathes that insulate many of their nerve cells. In both mice and humans, disruption of these sheathes' integrity impairs the ability of the long, cable-like nerve cells they surround to transmit signals. This, in turn, can produce a bevy of effects from loss of muscle control to blindness to attention and cognition deficits.

The Alzheimer's research community is greeting the news with equanimity: "Many substances made in the body can have vastly different functions under different circumstances," says Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease in San Francisco.

A-beta's toxicity within the brain has been established beyond reasonable doubt, Mucke says. But A-beta is made throughout our bodies all of the time. Even though it's been studied for decades, its normal function remains to be identified, he says. "Most intriguing, to me, is this peptide's potential role in modulating immune activity outside the brain."

Previously: Brain sponge: Stroke treatment may extend time to prevent brain damage, Two different types of MS, one big step toward personalized medicine and Stanford neuroimmunologist discusses recent advancements in MS research

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