Detecting Alzheimer's Early with Non-Invasive Optical Tools

Building upon the stunning recent discovery that Alzheimer's disease can be detected early by looking for telltale proteins in the eye, researchers at this week’s Frontiers in Optics meeting of the Optical Society of America presented a pair of optical tests, both in clinical trials, that can potentially diagnose the disease in its beginning stages. Such tests may not only improve patients' chances to start treatment earlier, but they could also speed development of new Alzheimer's drugs.

Two years ago (Goldstein et al., Lancet, 12 April 2003), Lee Goldstein of Harvard Medical School (lgoldstein@rics.bwh.harvard.edu) and his colleagues showed that the exact same amyloid beta proteins which are a hallmark of Alzheimer's disease are also found in the lens and its surrounding fluid. In those portions of the eye, the proteins form amyloid deposits similar to those in the brain. Furthermore, the researchers 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 (which are not at all associated with Alzheimer's).

Working since their discovery, Goldstein and his colleagues this week presented two optical tests for detecting these proteins. Using a technique known as quasi-elastic light scattering, the first test employs low-power infrared laser light to non-invasively detect protein particles in the specific part of the lens where these unusual cataracts form. The second test would be applied to those who screen positively for the proteins, in order to confirm an Alzheimer's diagnosis. This test uses a technique Goldstein and colleagues call "fluorescence ligand scanning" (FLS). The researchers apply special fluorescing eye drops with image-enhancing molecules that bind to the amyloid beta molecules. If amyloid beta molecules are present, the fluorescing molecules will light them up. The first test is in human and animal trials and the second test is in animal trials only.

These two diagnostic tests are envisioned to be a two-step process for screening and then confirming an Alzheimer's diagnosis. These new optical tools can also potentially speed up the development of new Alzheimer's drugs, by giving investigators rapid feedback on whether the drug is doing its job of removing the harmful proteins from the body. Moreover, the researchers are using the same technologies to develop new tests for rapidly detecting amyloid plaques resulting from prion diseases, including mad cow, scrapie in sheep, and Creutzfeldt-Jacob disease in humans.

The Frontiers in Optics meeting
Paper FTuBB4 at meeting, October 18, 2005