Early Detection, Early Treatment

Aug. 4, 2004 -- Early removal of plaque in the brain is the key to treating Alzheimer's disease, mouse studies suggest.

That's easier said than done, although several anti-plaque treatments are in the pipeline. But the new findings seem to resolve the chicken-or-egg question at the heart of Alzheimer's research.

That crucial question: Which of the two brain lesions found in Alzheimer's patients causes the disease? Is it the plaque that clogs the brain? Or is it the tangled protein that gums up nerve cells?

Frank LaFerla, PhD, and colleagues at the University of California, Irvine, say they have the answer.

"We've demonstrated in the lab that removing plaques from the brain can indeed lead to a total clearance of tangle pathology," LaFerla says in a news release.

The only downside is that the tangles only go away if treatment starts early. Once the tangles reach a certain stage, they stay stuck in the brain after plaque removal.

Plaque and Tangles

The brain uses protein messengers to send and receive various signals. Badly formed proteins act like a monkey wrench in the brain machinery. That's why the brain has a system for clearing away bad proteins.

But the amyloid proteins that make up Alzheimer's plaque somehow defeat this system. They clog up the works. That, LaFerla says, lets Alzheimer's tangles build up.

To prove it, LaFerla's team used a strain of mice that gets both Alzheimer's plaque and Alzheimer's tangles. When given an antibody that makes the immune system destroy plaque, the mouse brains become completely free of plaque. A little later, the tangles go away, too -- unless you wait too long. Once the tangles reach a certain point, even a plaque-free brain can't clear them.

Anti-tangle antibodies removed early tangles. But that didn't make the plaque go away. And the antibodies didn't work on advanced tangles.

The findings appear in the Aug. 5 issue of Neuron.

LaFerla says it's important to find ways to diagnose Alzheimer's disease in its earliest stages so anti-plaque treatments -- once they're perfected -- can work the best. He also says it's important to look for ways to clear late-stage tangles.

"These findings raise the intriguing possibility that a multi-antibody-based approach -- one targeted against [plaque] and one targeted against [tangles] -- may provide the most significant benefit for the treatment of Alzheimer's disease," LaFerla and colleagues write.

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