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Diagnosis is in the eyes, thanks to color-coded markers


SAN DIEGO – New fluorescent probes that change color when they encounter brain disease markers found in the eye could offer a simpler way to identify neurodegenerative disease and distinguish between closely related disorders such as Parkinson’s, Alzheimer’s and Creutzfeldt-Jakob.

Amyloids – sticky plaques of protein – mark several different but related brain diseases with overlapping symptoms. Methods for diagnosing and monitoring these disorders are not very advanced.

Among the few available diagnostics for Alzheimer’s disease are radioactive molecules that target amyloid, which can be detected in the brain using PET scans. This test shows whether amyloid has formed in the brain, but does not distinguish between the various diseases.

To overcome this obstacle, scientists at the University of California, San Diego, have created several fluorescent probes that change color depending on the type of amyloid they encounter. Because amyloids accumulate in the eyes as well as the brain, it is possible that neurodegenerative diseases could be differentially diagnosed with simple eye drops or ointment and an eye exam.

“The key trick here is that the small differences in the proteins that make up different forms of amyloid interact differently with our fluorescent probes to result in measurably different colors of the emitted light,” said Jerry Yang, co-leader of the project with Emmanuel Theodorakis; both are professors of chemistry and biochemistry at the university. Christina Sigurdson from the department of pathology at UCSD’s School of Medicine was a key collaborator.

The physical properties of the pockets in the various amyloid proteins determine the color change in the fluorescent probes. The team showed that one of the probes glows yellow when marking amyloid deposits associated with prion disease, whereas the same probe glows green when it binds to tissue samples with Alzheimer’s disease.

“We think that our approach represents a significant step toward developing diagnostics to distinguish between different, but closely related, diseases where symptoms and pathological characteristics show many similarities,” Yang said. “Such capability might prove to be very important for deciding on effective treatment strategies for specific diseases.”

The team is expanding its catalog of markers by creating probes that can discriminate between other amyloid forms. The technology has been licensed for commercial development of diagnostic tests for human neural disease.

The study appeared online in the Journal of the American Chemical Society (doi: 10.1021/ja3063698).

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