New dye could offer early test for Alzheimer’s
MIT technique is noninvasive
MIT scientists have developed a new dye that could offer noninvasive early diagnosis of Alzheimers disease, a discovery that could aid in monitoring the progression of the disease and in studying the efficacy of new treatments to stop it.
The work will be published in the Aug. 26 issue of Angewandte Chemie.
Today, doctors can only make a definitive diagnosis of Alzheimers-currently the fourth-leading cause of death in the United States-through a postmortem autopsy of the brain. “Before you can cure Alzheimers, you have to be able to diagnose it and monitor its progress very precisely,” said Timothy Swager, leader of the work and a professor in MITs Department of Chemistry. “Otherwise its hard to know whether a new treatment is working or not.”
To that end, Swager and postdoctoral associate Evgueni Nesterov, also from the MIT Department of Chemistry, worked with researchers at Massachusetts General Hospital and the University of Pittsburgh to develop a contrast agent that would first bind to the protein deposits, or plaques, in the brain that cause Alzheimers, and then fluoresce when exposed to radiation in the near-infrared range. The new dye could allow direct imaging of Alzheimers plaques through a patients skull.
Some of the first noninvasive techniques for diagnosing Alzheimers involved agents labeled with radioactive elements that could enter the brain and target disease plaque for imaging with positron emission tomography (PET). However, these methods were expensive and limited by the short working lifetime of the labeled agents.
Swager and colleagues developed the new dye, called NIAD-4, through a targeted design process based on a set of specific requirements, including the ability to enter the brain rapidly upon injection, bind to amyloid plaques, absorb and fluoresce radiation in the right spectral range, and provide sharp contrast between the plaques and the surrounding tissue. The compound provided clear visual images of amyloid brain plaques in living mice with specially prepared cranial windows.
To make the technique truly noninvasive, scientists must further refine the dye so it fluoresces at a slightly longer wavelength, closer to the infrared region. Light in the near-IR range can penetrate living tissue well enough to make brain structures visible. Swager likens the effect to the translucence produced when one holds a red laser pointer against the side of a finger.
“This procedure could be done in a chamber with a photodetector and a bunch of lasers, and it would be painless,” he said, adding that infrared fluorescence and other optical techniques will lead to a whole new class of noninvasive medical diagnostics. Swager says fluorescing dyes like NIAD-4 could be ready for clinical trials in the near future.
“What we have is a dye that lights up when it binds to amyloids that form in the brains of people with Alzheimers. Its a completely new transduction scheme-a way of translating a physical or chemical event thats invisible to the naked eye, into a recognizable signal. Further wavelength adjustments in these dyes will allow us to perform in vivo analysis through human tissue.”
The new dye was developed as part of a broader effort in sensing technology at MITs Institute for Soldier Nanotechnologies. In addition to its applications as a medical diagnostic, Swager says fluorescing dyes like NIAD-4 could work as signals in a wide variety of sensing schemes.
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