Eyes Might Hint at Alzheimer's

Two noninvasive tests detect telltale protein in the lens, researchers say

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By Amanda Gardner
HealthDay Reporter

TUESDAY, Oct. 18, 2005 (HealthDay News) -- Two tests may one day be able to diagnose Alzheimer's disease by detecting beta amyloid protein in the eye.

"We have developed a series of techniques that very, very sensitively and quantitatively and noninvasively track beta amyloid in the lens," said research leader Dr. Lee Goldstein, director of the molecular aging and development lab at the Center for Ophthalmic Research at Brigham and Women's Hospital in Boston. "The idea is to use this as a window to what's going on in the brain, and to pick up the pathology before it is manifested."

The findings are being presented Tuesday at the Optical Society of America annual meeting in Tucson, Ariz.

There is currently no definitive diagnostic test for Alzheimer's, a devastating disease of aging that robs a person of his or her memory and cognitive abilities. This has hindered early treatment strategies, as well as the development of new drugs. With no way to tell if a person actually has Alzheimer's, there is no way to tell if a new drug is actually working.

A build-up of amyloid beta protein in the brain is a hallmark of the disease and many researchers have been trying to find ways to detect the protein elsewhere in the body, including the eye.

"People have looked at the eye off and on for years to try and find clues to diagnose Alzheimer's," said Dr. Sam Gandy, chairman of the Medical and Scientific Advisory Council of the Alzheimer's Association and director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia. "Everyone would like to make a diagnosis with greater certainty and earlier. The eye, being an extension of the brain, is a tempting place to look."

In 2003, Goldstein and his colleagues published work detailing the presence of amyloid beta in the eye.

"This is the first time that Alzheimer's amyloid has been found outside the brain," Goldstein explained. "What we're saying is that Alzheimer's is a systemic disorder, not restricted to the brain, although it's mostly a brain disease."

In this case, the lens of the eye, like the brain, actually produces its own amyloid beta. "The process that's going on in the brain is also going on in the eye," Goldstein said. The researchers also discovered that the amyloid beta proteins in the lens produce a very unusual cataract, formed in a different place in the eye than common cataracts.

Since then, Goldstein has been on a quest to develop new technologies to take advantage of that finding. Details of two investigational techniques are being presented at the optical society meeting.

The first, quasielastic light scattering (QLS), is used in physics and in the commercial world to measure the quantity and size of very small particles in the air. The instrument devised by Goldstein and his colleagues can be used on patients. It utilizes low-wattage infrared lasers, and is safe, he said.

"We shine the light in. There's a brief pulse. It takes less than a second," Goldstein said. "It will give us information about the molecular pathology of the lens."

While the first test contributes sensitivity, the second test contributes specificity, or the ability to tell if the particles being detected really are amyloid. The researchers use an ointment that binds to the amyloid that would be given to individuals who screen positively on the first test. Because the technique, called "fluorescence ligand screening," requires regulatory approval, it is even further away from prime time.

"The two are entirely complementary techniques," Goldstein said.

Gandy said: "The basic premise does have some novelty and credibility over some of the previous studies. At least this is a molecule that we know circulates throughout the body and we know it is involved in the pathology of the disease, so from that point of view, it's interesting."

Goldstein is hoping that the techniques may help solve several important problems, including that of finding effective drugs. "The drug-development pipeline is quite extensive at this point, and the major problem is the lack of a diagnostic. That's a real roadblock," he said.

It's difficult to pick out which patients have Alzheimer's and which are "normal" for the control group. Even if there are no symptoms, an apparently healthy person could have incipient Alzheimer's. "Patient stratification is a real nightmare," Goldstein said.

It's also difficult to follow the progression of the disease as symptoms are often at odds with the degree of pathology in the brain.

Finally, Goldstein said, "we want to be treating patients before they have any cognitive symptoms. We don't want to treat them when they have Alzheimer's disease because in my estimation, it's going to be much harder to turn back the clock than to slow the progression. Treatment is going to demand therapy and a diagnosis. They're tied together."

Goldstein also thinks the emerging tools have promise for diagnosing prion diseases such as Creutzfeldt-Jacob disease. Prion diseases are also amyloid disorders.

More information

Visit the Alzheimer's Association for more on diagnosing this disease.

SOURCES: Sam Gandy, M.D., Ph.D., chairman, Medical and Scientific Advisory Council, Alzheimer's Association, and director, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia; Lee Goldstein, M.D., Ph.D., director, molecular aging and development lab, Center for Ophthalmic Research, Brigham and Women's Hospital, and assistant professor, psychiatry, Harvard Medical School, Boston; Oct. 18, 2005, presentation, Optical Society of Amercian annual meeting, Tucson, Ariz.

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