New Dye Could Offer Early Test for Alzheimer's

MIT scientists have developed a new dye that could offer noninvasive early diagnosis of Alzheimer's disease, a discovery that could aid in monitoring the progression of the disease and in studying the efficacy of new treatments to stop it.

MIT scientists have found a new way to monitor Alzheimer's disease using a fluorescent marker (“bubbles” in the background). The dye enters the brain after an intravenous injection and selectively binds to the plaques associated with the disease. Subsequent scanning with a near-infrared laser beam (hv) makes it possible to monitor the plaques through the characteristic fluorescence of the dye (black circle). (Evgueni Nesterov)

Today, doctors can only make a definitive diagnosis of Alzheimer's-currently the fourth-leading cause of death in the United States-through a postmortem autopsy of the brain.

Researchers at 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 Alzheimer's, and then fluoresce when exposed to radiation in the near-infrared range. The new dye could allow direct imaging of Alzheimer's plaques through a patient's skull.

Some of the first noninvasive techniques for diagnosing Alzheimer's 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.

The new dye, called NIAD-4, was developed 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.

Visit http://web.mit.edu/isn,