NCPA - National Center for Policy Analysis


August 11, 2006

Scientists have discovered molecular janitors that clear away a sticky gunk blamed for Alzheimer's disease -- until they get old and quit sweeping up.  The finding helps explain why Alzheimer's is a disease of aging.  More importantly, it suggests a new weapon: drugs that give nature's cleanup crews a boost.

The discovery, published by the journal Science, was made in a tiny roundworm called C. elegans.  What do worms have to do with people?  They're commonly used in age-related genetics research, and the new work involves a collection of genes that people harbor, too. 

Thursday's study reveals one way that cells fend off amyloid buildup, and that natural aging gradually erodes that detoxification process.

  • Worms can't get Alzheimer's so researchers used roundworms that produce human beta-amyloid in the muscles of the body wall.
  • As the worms age, amyloid builds up until it eventually paralyzes them; they can wiggle only their heads.
  • Then the researchers altered genes in a pathway called insulin/IGF-1, long known to be key in controlling lifespan.
  • Making the worms live longer protected them from paralysis.

So in slowing down normal aging, something also slowed the buildup of toxic amyloid. But what?  Enter those cellular janitors, two proteins in that gene pathway:

  • One, named HSF-1, breaks apart amyloid and disposes of it, the researchers discovered. Natural aging slows HSF-1, so it can't keep up with the necessary detoxification.
  • Another protein called DAF-16 jumps in to help buy a little more time, by clumping extra amyloid together in a way that makes it less toxic.

Scientists already are creating drugs to try to rid the brain of amyloid.  These cleanup proteins point to a novel way to do that.  The hope: Create drugs that boost their effects, and amyloid might not build up in the first place.

Source: Lauran Neergaard, "Scientists Make Discovery in Alzheimer's," Associated Press/, August 10, 2006.


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