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Researchers may have found a way to diagnose Alzheimer's disease with a couple of simple eye tests. As this ScienCentral News video explains, this could one day offer the chance to catch the disease early.
Seeing Eye to Eye with Alzheimer's
As we continue to live longer we are becoming more and more prone to age-related diseases, such as the so-called big four: heart disease, cancer, diabetes and Alzheimer's disease or AD.
Although an estimated 4.5 million Americans are believed to have AD, the only way to know for sure is with an autopsy. "Alzheimer's disease is a very difficult disorder to diagnose even in the late stages," explains Alzheimer's researcher Lee E. Goldstein from the Brigham and Women's Hospital and Harvard Medical School in Boston. "If we're going to intervene early, we're going to have diagnose it early. Right now there is no good way to do that."
We know a great deal about this disease primarily from what genetics research has told us over the last ten years. But a biomarker or a "biological fingerprint" is needed to help doctors spot the disease early. "We don't have good biomarkers for Alzheimer's disease: used not only for prediction and diagnosis, but also used for drug testing. If you want a way to screen to see how well the patient's doing beyond cognitive testing, if you want some kind of measure of whether the brain is being helped — using some kind of representative marker — we don't really have much in that way in Alzheimer's disease," says Goldstein's colleague from Massachusetts General Hospital and Harvard, Rudolph Tanzi, who was one of the geneticists to uncover the first disease-related genes.
Goldstein and his colleagues have developed a two-step process for screening for AD — two complementary techniques that can detect the build up of fragments of an AD-related protein, called beta amyloid, in the lens of the eye. This offers the potential to diagnose the disease early, improving patients' chances to start treatment early, as well as helping to speed the development of new AD drugs.
"The eye is a window on the brain, literally and figuratively, here. And we're able to look at the same disease process in Alzheimer's disease by looking at it in the eye," says Goldstein.
Brain of Alzheimer's patient filled with beta amyloid build-up. image: National Institute on Aging
Previously it was believed that the beta amyloid proteins only build up in the brain. "Intents to find beta amyloid outside the brain were unsuccessful," explains Tanzi.
But a few years ago, Goldstein's research team discovered the same beta amyloid proteins in the lens of the eye of AD patients. The buildup of these proteins produces a very unusual cataract in the lens — it doesn't obscure vision, and is very distinct from the usual age-related cataracts (which are not at all associated with AD). "My team had been studying Alzheimer's disease and we noticed, actually quite by chance, that some of our laboratory animals that had Alzheimer's disease also had a very unusual cataract," he says. "The cataract that we're looking at is actually way out at the edges of the lens of the eye."
As Goldstein reported at the 89th Annual Meeting of the Optical Society of America, Frontiers in Optics 2005, in Tucson, Arizona, they have developed two complimentary optical tests for detecting these proteins.
Using a technique known as quasielastic light scattering, the first test employs a harmless, low-powered, infrared laser to non-invasively detect protein particles in the lens. "Essentially this is a technique that uses entirely safe laser pulse. Very briefly, it's directed into the lens of the eye and then we collect what's called 'back-scattered light' on the other side and we're able to determine… how much beta amyloid is in the lens of the eye," Goldstein explains. "From the patient's perspective, this feels very much like a test that they would have in a regular ophthalmologists office. It's very brief, entirely safe, very simple."
He says the technique takes advantage of the same principle that explains why clouds in the sky appear white. "There are particles in the lens just as there are particles in the clouds. The particles in the clouds turn out to be water, and the particles in the eye turn out to be this protein. And when we direct light to interact with these particles, what happens is we get light back and it appears white. That's why a cloud appears white in the sky and this is why the lens appears white in Alzheimer's disease," Goldstein explains.
Their second test biochemically confirms the diagnosis for those patients who screened positive with the first test. Goldstein uses specially designed eye drops that bind to the amyloid molecules and light up, or fluoresce, to confirm their location at the edge of the lens.
It's generally believed that the amyloid accumulates in the lens long before it starts to build up in the brain. "We're validating that now and we've developed techniques that are extremely sensitive. They'll pick up this process before we even see the cataracts," says Goldstein. "So we fully expect to be able to pick this up perhaps, hopefully, decades before we see symptoms that occur due to Alzheimer's disease in the brain."
Tanzi points out that the amyloid plaques in the brain are pretty big. "So while a plaque could take up to ten years to form, as soon as amyloid-beta starts to accumulate in the eye, it's going to start interacting with other proteins in the eye and you're going to start getting the cataract," he says. "The guess is that they're starting to form before symptoms occur."
Goldstein says it's hard to predict how soon his test will be able to help patients, but he hopes it will be available to doctors within the next two years.
His tests may also be able to shed some light on easy and early diagnosis of certain other diseases. "We are now doing collaborative research to investigate the possibility of using these types of techniques for prion diseases, in particular mad cow disease in cattle, scrapie in sheep and Cruetzfeld-Jacob disease in people," Goldstein says.
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