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CU Researcher Probing Links To Alzheimer's Using Tiny Wormm

University of Colorado at Boulder

A novel set of genetic experiments at the University of Colorado at Boulder on a worm species smaller than a human eyelash may help researchers better understand Alzheimer's and perhaps even lead to new treatments for the disease.

Christopher Link, a research associate at the Institute for Behavioral Genetics, said the nematodes were injected with a portion of a human gene known as beta amyloid, which has been linked to Alzheimer's in humans. Beta amyloid is a major component of abnormal protein deposits in the brain also called "senile plaque," which is considered the pathological hallmark of Alzheimer's victims, Link said.

Beta amyloid is believed by researchers to cause degeneration in the brain's nerve cells. "We want to know why beta amyloid accumulates and why it kills the neurons," said Link. "Ideally, we would like to see a treatment developed to block one effect or the other and slow the onset of the disease," he said.

The human gene segment inserted into the worms caused them to produce the protein for beta amyloid in their muscle cells, he said. The protein expressed by the human gene sparked the accumulation of plaque in the worms' muscle cells similar to the plaque in the brains of Alzheimer's victims.

Link took the project a step further by inserting a second gene into the worms known as a "reporter gene." Cloned from a jellyfish species, the reporter gene causes worm tissue to glow when under stress. The glowing muscle cells of worms containing both the beta amyloid and reporter genes allow researchers to track the toxicity of the beta amyloid in the transparent worms, Link said.

Link hopes the unique, "dual-transgenic" worms can be used to speed the search for drugs to treat Alzheimer's sufferers. "One could conceivably use these animals to screen for drugs that may block the formation of the plaque."

He recently disclosed his invention to CU-Boulder's Office of Technology Transfer and Industry Outreach, which helps campus inventors in the first steps of patenting. A patent has been filed and licenses are available through the University Technology Corp., a private company retained to market and license university inventions.

Cavities of dying neurons found in the bodies of Link's genetically manipulated nematodes appear to be similar to clumps of degenerated neurons in the brains of Alzheimer's victims, he said. The human beta amyloid proteins in the worms may be causing oxygen stress, causing the cell receptors to malfunction.

The nematode, known as C. elegans, has become the worm of choice for many genetic researchers in recent years. Of the roughly 8,000 genes identified in the worm, at least 40 percent appear to have human counterparts, scientists believe. Human and C. elegans genes are so closely related that a human gene can sometimes restore normal function to a mutant worm cell. "There is a lot of evidence that genes in people and in these worms work the same way," Link said.

"We are developing a model to explain how the plaque accumulates and why it is toxic," he said. "The main goal now is to determine the degree of relevance this particular line of research has to humans," said Link, whose research is funded by the National Institutes of Health.

Alzheimer's is estimated to affect between 2 million and 4 million people in the United States, and about 100,000 people die from it each year. Mortality from the disease increased about 10-fold from 1979 to 1989.

Scientists have recently identified several genes that affect the susceptibility of people to Alzheimer's, said Link. Victims of the disease typically suffer from such symptoms as progressive memory deficit, a decline in cognitive function, anxiety, depression, speech deficits and personality changes.


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