Similarity found with destructive protein behind mad cow

By Laura Sanders

Web edition: December 13, 2012
Print edition: December 29, 2012; Vol.182 #13 (p. 24)

2012 SCIENCE NEWS TOP 25: 10

An infectious, self-replicating protein might be at the heart of Alzheimer’s disease, a growing number of studies suggest. If correct, this idea could change how scientists view the condition, which affects 5.4 million Americans.

A tiny seed of a dangerous protein could corrupt other harmless proteins, the theory goes, creating and unleashing a destructive army in the brain. And this process might not be restricted to Alzheimer’s. Some researchers believe the spread of such proteins in the brain could explain other devastating disorders such as Parkinson’s, Huntington’s disease and amyotrophic lateral sclerosis.

In Alzheimer’s, the possible infectious agent under scrutiny is a protein called amyloid-beta, best known as the main ingredient in the hulking, sticky gobs of plaque found in the brains of people with the disease. It turns out that A-beta probably causes damage long before it accumulates into these plaques. Smaller arrangements of A-beta, called oligomers, scramble brain messages and eventually kill nerve cells.

These oligomers, some scientists now believe, are infectious agents known as prions. Such self-replicating proteins, discovered 30 years ago by Stanley Prusiner of the University of California, San Francisco, are responsible for the brain-wasting Creutzfeldt-Jakob disease in people, scrapie in sheep and bovine spongiform encephalopathy in cattle. Over 20 years ago, Prusiner argued that something similar could be happening in Alzheimer’s and other brain diseases. In the last few years, he and others have turned up some evidence that his hunch could be right, and now more people are paying attention.

A-beta injected into half of a mouse’s brain slowly incites other A-beta molecules to accumulate, Prusiner and colleagues reported earlier this year (SN: 7/14/12, p. 5). And Swedish scientists caught A-beta jumping directly from nerve cell to nerve cell in rat and human cells in a dish, suggesting that the protein can follow neural connections in the brain.

Still more evidence comes from a study on a particularly dangerous form of A-beta. In “vanishingly small” quantities, this form, called pyroglutamylated A-beta, can cause normal versions of A-beta to turn deadly, says study coauthor George Bloom of the University of Virginia. These proteins needed just 24 hours to kill half of mouse nerve cells tested in a dish (SN: 6/2/12, p. 18).

If the prion idea is right, then over many years a small, dangerous A-beta seed may cause harmless forms of A-beta to shape-shift into a destructive form of the protein. So far, there’s no direct evidence of this shift in people, but scientists are looking.

Thinking of Alzheimer’s as a prion disease could have big implications for how to slow its progress or even prevent it. New approaches might aim either to keep destructive forms of A-beta out of the brain or to interrupt their spread. 

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