Researchers have developed a new chemical that makes it possible to peer inside the brain, distinguishing between people who have healthy brain function from those suffering from various stages of memory loss or Alzheimer's disease. The compound, called FDDNP, could be used with brain scans that allow for the diagnosis of Alzheimer's at the earliest stages, when drugs or other therapies may be most effective. This method could also provide a new way to monitor the effectiveness of various treatments for the disease.
The chemical, developed by doctors at the University of California in Los Angeles, attaches to clumps of abnormal brain tissue called beta amyloid plaques and tau tangles. Plaques and tangles are hallmarks of Alzheimer's disease and appear in the brain at the very earliest stages of illness, before memory loss becomes severe. As they build up in the brain, healthy brain cells gradually lose the ability to communicate with one another and die off, and memory fades. At present, doctors diagnose Alzheimer's by a process of elimination, by ruling out the testable causes of a patient's dementia. A definitive diagnosis can only be made at autopsy when brain tissue is analyzed directly.
In the study, doctors used an advanced imaging technique called PET, or positron emission tomography, to scan the brains of 83 volunteers who had been given injections of FDDNP. They ranged in age from 49 to 84. About a third of the study participants were mentally alert and healthy. The others had suspected Alzheimer's disease or mild cognitive impairment (MCI), which often progresses to Alzheimer's. MCI is not the same as the more common type of age-associated forgetfulness that does not progress to Alzheimer's.
The PET scans picked up the presence of FDDNP in the brain, forming "lit-up" images in areas where plaques and tangles had formed. Few highlighted areas appeared in healthy individuals, and larger areas appeared in those with mild cognitive impairment. In people diagnosed with Alzheimer's, much of the brain showed FDDNP involvement, indicating high levels of plaques and tangles. The more advanced the disease, the higher the concentrations of FDDNP in the brain.
The scans were done over a two-year period and were able to pick up the progressive deterioration of brain function. "We could see the definitive patterns starting early in patients with mild cognitive impairment and advancing in those with Alzheimer's disease," said Dr. Jorge Barrio, one of the study's authors and a professor at the David Geffen School of Medicine at UCLA.
The test was 98 percent accurate in detecting the difference between full-blown Alzheimer's and mild cognitive impairment. These results were far more accurate than traditional PET scans, which measure the way the brain processes sugars, or other imaging techniques, such as MRI (magnetic resonance imaging).
The FDDNP-PET scan test also detected brain problems in people years before they developed Alzheimer's disease. Such early detection could be useful for doctors, because future drugs and other therapies may be most effective in the earliest stages of Alzheimer's disease, before plaques and tangles build up to critical levels. The technique could also help doctors test various experimental treatments for the disease to see if they are having beneficial effects on brain function.
At this point, the new PET scans remain an intriguing research tool. Far more people will need to be tested before the test becomes commercially available, and testing will likely take several years. Still, some 4.5 million Americans have Alzheimer's disease, and 15 to 20 million have mild cognitive impairment. An effective early test would be an indispensable tool for the diagnosis and management of Alzheimer's.
Other diagnostic tests are also under development. [See the article, "Protein 'Fingerprint' May One Day Lead to an Alzheimer's Test."] The Fisher Center for Alzheimer's Research Foundation continues to offer vital funding to medical researchers around the country, and around the world. To learn more about this exciting research and ways you can help in the fight for a cure, visit www.Alzinfo.org.
Gary W. Small, M.D., Vladimir Kepe, Ph.D., Linda M. Ercoli, Ph.D., et al: "PET of Brain Amyloid and Tau in Mild Cognitive Impairment." New England Journal of Medicine, Volume 355, Number 25, December 21, 2006, pages 2652-2663.