Scientists Reveal What May Cause Alzheimer's: Beta-Amyloid

Alzheimer's disease continues to remain a major health concern across the U.S. and the world. Now, though, scientists have learned a little bit more about this disease. They've shown how a protein fragment known as beta-amyloid, strongly implicated in Alzheimer's disease, begins destroying synapses before it clumps into plaques that lead to nerve cell death. The findings could help researchers better understand exactly how Alzheimer's develops in patients.

In order to better understand Alzheimer's, the researchers used experimental mice that are highly susceptible to the synaptic and cognitive impairments of the disease. The scientists found that if the mice lacked a surface protein ordinarily situated very close to synapses, they were resistant to the memory breakdown and synapse loss associated with the disorder. In fact, the researchers discovered that this protein, called PirB, is a high-affinity receptor for beta-amyloid in its soluble cluster form. In other works, the soluble beta-amyloid clusters stuck to PirB quite strongly.

Beta-amyloid begins life as a solitary molecule but eventually begins to bunch up. At first, it forms small clusters that are still soluble and can travel freely in the brain. Eventually, though, they create the plaques that are so well-known in Alzheimer's.

When the soluble clusters stick to PirB, though, something interesting happens. It trips off a cascade of biochemical activities that culminate in the destruction of synapses. Synapses are the connections between nerve cells and are essential for storing memories, processing thoughts and emotions and planning and ordering how we move our bodies.

The next step was to eliminate PirB from the Alzheimer's mouse strain. Researchers wanted to see whether eliminating this protein would restore the brain's flexibility. In the end, they found that the brains of young "Alzheimer's mice" in which PirB was absent retained as much synaptic-strength-shifting flexibility as normal mice.

"The PirB-lacking Alzheimer's mice were protected from the beta-amyloid-generating consequences of their mutations," said Carla Shatz, one of the researchers, in a news release.

After further experimentation, the researchers found that PirB and beta-amyloid were binding. This caused PirB to stomp on the brakes even more than it usually does, weakening synapses so much that they could disappear altogether, taking memories with them.

The findings are important for better understanding the development of Alzheimer's in patients. This, in turn, could allow researchers to develop better treatments. For example, soluble PirB fragments containing portions of the molecule that could act as a decoy might be able to exert a therapeutic effect.

The findings are published in the journal Science.