Researchers may have hit upon a strategy to prevent or treat Alzheimer’s disease - although the technique has only been tested in the lab at this point.

The signature of Alzheimer’s is the accumulation of plaques and tangles made up of abnormal amyloid protein, called amyloid beta, in the brain. The amyloid beta aggregations are toxic to nerve cells, and some way of stopping this clumping-together is needed.

“To approach this problem, we envisioned a Trojan horse strategy,” Dr. Isabella A. Graef and colleagues write in the journal Science.

The pathologists, from Stanford University Medical School in California, created “a small bifunctional molecule” that can bind to amyloid beta and at the same time latch on to a large “chaperone” protein. The intention was to create an entity bulky enough to stop amyloid beta proteins forming plaques.

The team synthesized the key “linker” molecule by combining the dye Congo red, which is absorbed by amyloid, with an artificial structure that attaches to a large protein called FKBP.

In a lab dish, low concentrations of the resulting three-part molecule virtually prevented beta amyloid from forming fibrils, although it was still able to form small aggregates.

The researchers next showed that neurons growing in culture were damaged or killed by beta amyloid, but neurotoxicity was significantly reduced by the addition of the new compound.

Graef’s group concludes that “the recruited-chaperone approach might provide a viable complement” to other research efforts to prevent amyloid beta accumulation in Alzheimer’s disease.

However, it will be some time before this technology has clinical application, a chemist at Harvard Medical School in Boston comments in a Science news release. For one thing, Dr. Peter Lansbury points out, Congo red does not enter cells or cross the blood-brain barrier so another component of the linker molecule will have to be found.

SOURCE: Science, October 29, 2004.