Breakthrough Brain Imaging-agent Enables Researchers To See Amyloid Plaques in People with Alzheimer's Disease
Discovery has potential for accelerating the pace of Alzheimer research
Stockholm?The first human studies of a promising compound used with Positron Emission Tomography (PET) imaging indicate that researchers now can, for the first time, successfully highlight amyloid plaques in the brains of individuals in the early stages of Alzheimer's disease.
"Having the ability to quantify amyloid deposition in the brain will have a profound impact on our ability to monitor the progression of Alzheimer's as well as gauge the effectiveness of medical treatments," said William Thies, Ph.D., vice president of medical and scientific affairs for the Alzheimer's Association.
Prior to this discovery, the scientific community was unable to view amyloid plaques -- one of the pathological hallmarks of Alzheimer's -- in a person living with the disease. Only during autopsy could researchers use special stains to highlight the mind-robbing amyloid plaques for further investigation.
The scientific collaboration leading to this breakthrough has taken place over the course of 10 years, beginning with researchers at the University of Pittsburgh School of Medicine, under the leadership of Professor of Radiology Chester Mathis, Ph.D. Mathis and his colleagues synthesized more than 100 compounds and examined their properties to identify an agent that could safely cross the blood-brain barrier membrane that controls the entry of substances from the blood into the brain.
After conducting research using synthetic amyloid fibrils, normal mice and normal non-human primate species (baboons), they selected the compound 6-OH-BTA-1, based on its ability to bind specifically to amyloid plaques, cross the blood brain barrier, and clear from normal brain tissue. The compound's successful demonstration of these properties led researchers to conclude that the imaging agent held promise for use in studying individuals with Alzheimer's disease.
The next phase of this research involved the Pittsburgh team and Drs. Brian Bacskai and Brad Hyman at Massachusetts General Hospital. Using microscopic "multiphoton" imaging technology and transgenic mice - mice genetically engineered to develop amyloid plaques similar to those in Alzheimer's disease - researchers were able to inject the compound into a vein of the mice and see individual amyloid plaques as they came in contact with the 6-OH-BTA-1 compound. This work was a critical link to the compound's viability for human studies as it showed that the compound actually distinguishes individual amyloid plaques in the brain of a living animal model of Alzheimer's disease.
Building on the research conducted at the University of Pittsburgh, Bengt Langstrom, professor of organic chemistry, Uppsala University PET Center, led colleagues from the PET Center and Karolinska Institutet, Huddinge, Sweden, in the first human amyloid imaging studies.
Fourteen individuals were recruited for the Uppsala study, where researchers refer to the compound as "Pittsburgh Compound B" or PIB. Nine of the participants range in age from 55 to 70, have a diagnosis of Alzheimer's, and are in relatively mild stages of the disease. Five additional individuals with no cognitive impairment were selected to serve as the controls.
After receiving the compound intravenously, the study participants underwent a 60-minute PET scan. While the patients lay immobile for the duration of the scan, scientists were able to gather valuable images that showed that the compound entered the brain without problem and was retained in specific regions of the brain consistent with the accumulation of plaques previously only seen during autopsy in the brains of people with Alzheimer's disease. In addition, the researchers found that very little of the compound was retained in the brains of the control individuals who had no cognitive impairment.
According to Langstrom, who is also managing director of Uppsala Research Imaging Solutions AB (URIS), "This research, which has been conducted very carefully over several years, is especially promising for the development of new treatments in that there is now a tool that can be used to validate and expand our understanding of the mechanisms of this disease."
The Alzheimer's Association and National Institute on Aging provided grant support for the research conducted at University of Pittsburgh.
The Alzheimer's Association is hosting the 8th International Conference on Alzheimer's Disease and Related Disorders, July 20-25, 2002, in Stockholm, Sweden. The conference is the largest gathering of Alzheimer researchers in history. As many as 4,000 researchers from around the world will present and discuss the findings of nearly 2,000 studies on the prevention, diagnosis and treatment of Alzheimer's disease.
The Alzheimer's Association is the premier source of information and support for the millions of Americans with Alzheimer's. The largest private funder of Alzheimer research in the United States, the Association has committed $138 million toward research into the disease.
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