New Dye Could Offer Early Test For Alzheimer's; MIT Technique Is Noninvasive

The work will be published in the Aug. 26 issue of Angewandte Chemie.

Today, doctors can only make a definitive diagnosis ofAlzheimer's-currently the fourth-leading cause of death in the UnitedStates-through a postmortem autopsy of the brain. "Before you can cureAlzheimer's, you have to be able to diagnose it and monitor itsprogress very precisely," said Timothy Swager, leader of the work and aprofessor in MIT's Department of Chemistry. "Otherwise it's hard toknow whether a new treatment is working or not."

To that end, Swager and postdoctoral associate EvgueniNesterov, also from the MIT Department of Chemistry, worked withresearchers at Massachusetts General Hospital and the University ofPittsburgh to develop a contrast agent that would first bind to theprotein deposits, or plaques, in the brain that cause Alzheimer's, andthen fluoresce when exposed to radiation in the near-infrared range.The new dye could allow direct imaging of Alzheimer's plaques through apatient's skull.

Some of the first noninvasive techniques for diagnosingAlzheimer's involved agents labeled with radioactive elements thatcould enter the brain and target disease plaque for imaging withpositron emission tomography (PET). However, these methods wereexpensive and limited by the short working lifetime of the labeledagents.

Swager and colleagues developed the new dye, called NIAD-4,through a targeted design process based on a set of specificrequirements, including the ability to enter the brain rapidly uponinjection, bind to amyloid plaques, absorb and fluoresce radiation inthe right spectral range, and provide sharp contrast between theplaques and the surrounding tissue. The compound provided clear visualimages of amyloid brain plaques in living mice with specially preparedcranial windows.

To make the technique truly noninvasive, scientists mustfurther refine the dye so it fluoresces at a slightly longerwavelength, closer to the infrared region. Light in the near-IR rangecan penetrate living tissue well enough to make brain structuresvisible. Swager likens the effect to the translucence produced when oneholds a red laser pointer against the side of a finger.

"This procedure could be done in a chamber with a photodetectorand a bunch of lasers, and it would be painless," he said, adding thatinfrared fluorescence and other optical techniques will lead to a wholenew class of noninvasive medical diagnostics. Swager says fluorescingdyes 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 amyloidsthat form in the brains of people with Alzheimer's. It's a completelynew transduction scheme-a way of translating a physical or chemicalevent that's invisible to the naked eye, into a recognizable signal.Further wavelength adjustments in these dyes will allow us to performin vivo analysis through human tissue."

The new dye was developed as part of a broader effort insensing technology at MIT's Institute for Soldier Nanotechnologies. Inaddition to its applications as a medical diagnostic, Swager saysfluorescing dyes like NIAD-4 could work as signals in a wide variety ofsensing schemes.