PET, CFS Analysis May Predict Alzheimer's

Combining brain scanning with a new imaging agent and cerebrospinal fluid (CSF) analysis has given neuroscientists hope that they may finally be to diagnose Alzheimer's disease (AD) 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,” explained Anne Fagan Niven, Ph.D., research associate professor of neurology at Washington University School of Medicine (St. Louis, MO, USA). "Up to 30% 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.”

Dr. Fagan and colleagues evaluated a group of 24 individuals that included individuals diagnosed with very mild and mild AD, and cognitively normal control subjects. As predicted, in patients with cognitive impairments thought to be attributable to AD, investigators found low CSF levels of amyloid beta 42 (A-beta 42), the main component of the brain plaques that are characteristic of AD. In the same individuals, positron emission tomography (PET) scanning of the brain with a new imaging agent revealed the presence of amyloid plaques in the brain that were positive. What scientists did not expect was that three cognitively normal individuals would have both low CSF levels of A-beta 42 and positive results from the brain scans. Dr. Fagan stressed that even though this facet of their findings was very intriguing, it does not prove that the three normal controls will one day develop clinical AD.

Many earlier studies have found that A-beta 42 levels decrease in the CSF of AD patients. A-beta 42 is naturally produced in the brain, and scientists suspect that the creation of amyloid plaques may be tied to breakdowns of the processes that degrade or normally clear A-beta 42 from the brain via the CSF and the bloodstream. However, natural variations occur in CSF A-beta 42 levels in healthy individuals, and the amount this level decreases in Alzheimer's patients also varies. And that left no distinct level researchers could identify as a diagnostic marker characteristic of AD.

Dr. Fagan wanted to see if useful distinctions could be made by combining information on CSF A-beta 42 levels with findings from the PET brain scans with a new imaging agent, PIB (for Pittsburgh compound B). Developed by researchers at the University of Pittsburgh (PA, USA), PIB temporarily adheres to amyloid plaques in the brain but washes clean in 30 to 60 minutes. Scientists can detect this sticking with a PET scanner.