A combination of brain scanning with a new imaging agent and cerebrospinal fluid (CSF) analysis has left neuroscientists encouraged that they may finally be moving toward techniques for diagnosing Alzheimer's disease before its clinical symptoms become apparent.
"When clinical symptoms start, the disease process has already been at work in the patient for many years and possibly even decades," explains Anne Fagan Niven, Ph.D., research associate professor of neurology at Washington University School of Medicine in St. Louis. "Up to 30 percent of neurons in vulnerable areas are already dead, and you can't get them back. So finding markers that can help us identify patients prior to symptoms is really our big push now."
With colleagues Mark Mintun, M.D., professor of radiology, and David Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology, Fagan studied a group of 24 people that included individuals diagnosed with very mild and mild Alzheimer's disease, and cognitively normal subjects. As expected, in patients with cognitive impairments, believed to be attributable to Alzheimer's disease, researchers found low CSF levels of amyloid beta 42 (A-beta 42), the principal ingredient of the brain plaques that are characteristic of Alzheimer's disease. In the same individuals, brain scans with a new imaging agent that reveals the presence of amyloid plaques in the brain were positive. What scientists didn't anticipate was that three cognitively normal subjects would have both low CSF levels of A-beta 42 and positive results from the brain scans. Fagan stressed that although this aspect of their findings was very intriguing, it doesn't prove that the three normal subjects will one day develop clinical Alzheimer's disease.
"For now, definitive diagnosis of Alzheimer's disease still cannot be made until autopsy," she says. "It's going to take a number of years for us to fully assess these results, because all we can do now is follow the participants closely to see if they eventually develop Alzheimer's dementia." Fagan presents the results of the study at 10:15 a.m. on Nov. 15 at this year's annual meeting of the Society for Neuroscience in Washington, D.C. The study will also appear in an upcoming issue of Annals of Neurology. Many prior studies have found that A-beta 42 levels drop in the cerebrospinal fluid of Alzheimer's disease patients. A-beta 42 is naturally produced in the brain, and researchers suspect that the creation of amyloid plaques may be linked to breakdowns of the processes that degrade or normally clear A-beta 42 from the brain via the CSF and the bloodstream.