Alzheimer's disease can turn the brain into a biochemical garbage dump. Friday, scientists report for the first time just how normal cleanup might go awry.

A pathbreaking new study, published in the journal Science by researchers at Stanford Universiy, shows how toxic clumps of a defective protein can interfere with the routine hygiene system brain cells need to keep functioning into old age.

Experts said that the study, the latest in a vital field of brain research, points to the intriguing possibility that the same problem might be a culprit in many seemingly unrelated disorders, not just Alzheimer's.

The toxic clumps, consisting of a protein called amyloid-beta, are not necessarily the sole cause of Alzheimer's, or any other disease.

But the new finding, if it bears out in further research, could help scientists design a powerful blueprint for new therapies. Besides Alzheimer's, such an approach might also prove beneficial in Parkinson's and other common movement disorders arising from breakdowns in the nervous system.

``There's a sense this may be a common mechanism in a number of neurodegenerative diseases,'' said Bill Thies, vice president of medical and scientific affairs at the Chicago-based Alzheimer's Association.

But experts also warned that the work is still at the stage of basic research - and has yet to produce a single drug candidate. ``We're pretty early in terms of unraveling how this process works, so how to intervene at the clinical level is not immediately obvious,'' Thies said.

Brain cells grind up misshapen or otherwise unwanted proteins for disposal using a system of enzymes.

Study authors Neil F. Bence, Roopal M. Sampat and Ron R. Kopito found that clumps of amyloid gum up this cellular garbage disposal system. That allows still more clumps to form, causing even less efficient protein degradation.

Accumulated debris in brain cells can interfere with many basic processes the cells depend on to keep alive, and as they die, normal brain function becomes more and more difficult. The symptoms vary depending on which cells are affected and how many cells are wiped out.

Scientists said the breakdown in the cleanup system therefore could help explain the creeping memory loss of Alzheimer's, the worsening tremor of Parkinson's and the advancing paralysis of ALS, or amyotrophic lateral sclerosis, also known as Lou Gehrig's disease.

``What leaps out at anybody who studies any of these neurodegenerative diseases is that they all involve the formation of these protein aggregates,'' Kopito said.

He and his co-authors suggested the problem may not be peculiar to the brain, either. Essentially the same mechanism of cleanup-inhibition could be involved in cystic fibrosis, which affects breathing.

``This is an extremely interesting study,'' said Marcelle Morrison-Bogorad, associate director of a research program on the neuroscience of aging at the National Institute on Aging.

``What they're suggesting is a vicious circle,'' she added, in which cellular hygiene ``becomes less functional, degrading less protein, and therefore allows more protein to accumulate in these clumps.''

``Degradation and synthesis of proteins in cells have to be exquisitely balanced,'' she added. ``If something is inhibiting degradation, it's just like when your rubbish is not picked up every week. Very quickly you get into terrible trouble.''

A separate study, also appearing today in Science, from a team of Japanese researchers points to a potential new method to break up the faulty amyloid protein that forms the toxic clumps.

The presence of these clumps, or plaques, has long been known as a hallmark of advanced Alzheimer's and a worthwhile target of drugs, even though researchers were never quite sure if the amyloid clumps were a cause or merely a consequence of the disease.

So far, however, most drug researchers have tried to look for ways to block enzymes that help build the amyloid. The new study suggests a different strategy, involving an enzyme called neprolysin, which tears down amyloid.

Experts said the trick will be to find a drug or gene therapy capable of achieving that goal. It's often considered easier to block an enzyme than it is to rev one up.

``This is a harder target,'' said Louis Hersh, a biochemist at the University of Kentucky working in the same general field as the Japanese researchers. ``You've got an enzyme here that gets rid of amyloid-beta. The problem is how does one figure out how to increase the activity of an enzyme like this?''

There are no current strategies to do that in the case of amyloid-destroying neprolysin. But there are many efforts in the works along those lines, and even if a drug is not found right away, the latest study could also lead to earlier identification of genetic risk factors that make people vulnerable to the disease.

From Sfgate.com