Alzheimer's disease is the most common cause of late-life dementia. The disorder is thought to be caused by a protein known as the amyloid-beta protein, or Abeta, which clumps together in the brain, forming plaques that are thought to destroy neurons. This destruction starts early, too, and can presage clinical signs of the disease by up to 20 years.
For decades now, researchers have been trying, with limited success, to develop drugs that prevent this clumping. Such drugs require a "target" — a structure they can bind to, thereby preventing the toxic actions of Abeta.
Now, a new study out of UCLA suggests that while researchers may have the right target in Abeta, they may be missing the bull's-eye. Reporting in the Jan. 23 issue of the Journal of Molecular Biology, UCLA neurology professor David Teplow and colleagues focused on a particular segment of a toxic form of Abeta and discovered a unique hairpin-like structure that facilitates clumping.
"Every 68 seconds, someone in this country is diagnosed with Alzheimer's," said Teplow, the study's senior author and principal investigator of the NIH-sponsored Alzheimer's Disease Research Center at UCLA. "Alzheimer's disease is the only one of the top 10 causes of death in America that cannot be prevented, cured or even slowed down once it begins. Most of the drugs that have been developed have either failed or only provide modest improvement of the symptoms. So finding a better pathway for these potential therapeutics is critical."
The Abeta protein is composed of a sequence of amino acids, much like "a pearl necklace composed of 20 different combinations of different colors of pearl," Teplow said. One form of Abeta, Abeta40, has 40 amino acids, while a second form, Abeta42, has two extra amino acids at one end. Abeta42 has long been thought to be the toxic form of Abeta, but until now, no one has understood how the simple addition of two amino acids made it so much more toxic then Abeta40.