September 16, 2008
A type of brain scan known as positron emission tomography, or PET scanning, shows promise as a useful way to detect plaques in the brains of people with Alzheimer's disease, a new study found. In the trial, researchers injected patients with a radioactive dye called Pittsburgh Compound B that attaches to deposits of beta-amyloid, the toxic protein that builds up in the brains of those with Alzheimer's. PET scans of some of those subjects revealed that their brains contained plaques, areas of beta-amyloid buildup and damage that are a hallmark of Alzheimer's.
Currently, the most common and reliable way to assess the aggregation of beta-amyloid plaques in the brain is through analyzing brain tissue samples obtained at autopsy after a person with Alzheimer's dies.
In the study, researchers at the University of Kuopio in Finland and colleagues studied 10 patients who had undergone brain biopsies because they suffered from a condition called normal pressure hydrocephalus, caused by a buildup of fluids in the brain. None of them had severe memory loss or dementia, though they did show cognitive problems from the fluid buildup. About a quarter to a half of patients with symptoms of normal-pressure hydrocephalus have brain lesions characteristic of Alzheimer's disease.
Among the participants, six had beta-amyloid plaques in the tissue samples obtained, while four displayed no Alzheimer's disease--related brain changes. The patients were then injected with Pittsburgh Compound B and then underwent a 90-minute PET scan.
Results of the scans indicated that patients who had beta-amyloid plaques in their brain biopsy specimen displayed a higher uptake of Pittsburgh Compound B in certain brain areas than those who did not have such accumulations.
"This study supports the use of Pittsburgh Compound B in the evaluation of beta-amyloid deposition in, for example, mild cognitive impairment, Alzheimer's disease or normal-pressure hydrocephalus," the authors wrote. "Large and prospective studies are required to verify whether the Pittsburg compound will become a tool in diagnosing Alzheimer's disease."
The development of a test that could diagnose Alzheimer's at an earlier stage would be valuable because doctors could prescribe drugs to slow progression of the disease -- when such drugs are developed -- at an early stage, when they may be most useful. However, researchers know that many normal people without dementia show a buildup of beta amyloid plaques, as demonstrated by using the Pittsburg compound. Many of these people, however, may be at increased risk of developing Alzheimer's.
Early diagnosis could also allow researchers to test to see if experimental drugs are helping to prevent the progressive downward spiral that inevitably occurs in Alzheimer's. Disease progression, or remission, could be compared to changes in the beta-amyloid content of the brain. Instead of waiting until autopsy, such changes in the brain might be detected during life by the Pittsburgh compound, developed by researchers at the University of Pittsburgh Medical Center.
Further testing will be needed to confirm these findings. And it may take years before a reliable test to diagnose Alzheimer's disease at its earlier stages becomes routinely available at clinics across the country. In addition to Pittsburgh compound B, scientists are investigating other tests and brain imaging techniques to diagnose Alzheimer's at an earlier stage.
As those with relatives and friends of people with Alzheimer's know, the diagnosis of the disease is difficult to determine with certainty. An accurate test to diagnose Alzheimer's could help to predict the future course of symptom progression in people with the memory-robbing ailments.
A diagnostic test would also help researchers to monitor patients who are taking various medications, including experimental drugs. If brain scans showed that new deposits of beta-amyloid plaque were not growing in the brain, it might be a signal that a new Alzheimer's drug was working.
Ville Leinonen; Irina Alafuzoff; Sargo Aalto; et. al.: "Assessment of Beta-Amyloid in a Frontal Cortical Brain Biopsy Specimen and by Positron Emission Tomography With Carbon 11--Labeled Pittsburgh Compound B." Archives of Neurolology, Volume 65, Number 10, posted online August 11, 2008, doi:10.1001/archneur.65.10.noc80013.