Alzheimer’s-related plaques appear in brains of symptom-free adults

Fluorine-18 Pittsburgh Compound B, an imaging agent that could facilitate the early diagnosis of Alzheimer's disease, has been used to identify amyloid deposition in the brains of cognitively normal adults.

The findings could not only shed more light on how the illness progresses, but also open the door to possible prevention strategies, said senior investigator Dr. William E. Klunk, a professor of psychiatry and neurology at the University of Pittsburgh School of Medicine. They were reported in the November issue of the Archives of Neurology (2008;65[11]:1509-1517).

Klunk and colleague Chester A. Mathis, Ph.D., a professor of radiology and pharmaceutical sciences at Pitt, invented carbon-11 PIB, a radiopharmaceutical PET probe that binds to certain forms of amyloid protein plaques thought to destroy brain cells and considered a pathophysiological characteristic of Alzheimer's disease.

Before C-11 PIB PET/CT imaging, the deposits could be identified only during autopsy to confirm the diagnosis in hindsight.

The study, led by Dr. Howard J. Aizenstein, an associate professor of psychiatry and bioengineering at Pitt, identified amyloid deposits in the brains of nine of 43 volunteers (21%), aged 65 to 88 years, who showed no signs of cognitive deterioration associated with Alzheimer's disease or mild cognitive impairment, a suspected precursor of the disease.

The findings suggest that some elderly people harbor the early amyloid deposits but no visible symptoms of Alzheimer's disease.

"That means we might have a window of opportunity to slow or stop the process," Klunk said.

One surprising finding was that detailed tests of brain function showed no decrease in functioning among participants whose scans revealed the presence of the Alzheimer-associated amyloid deposits. The tests were conducted by study coauthors Robert D. Nebes, Ph.D., a professor of psychiatry, and Judith Saxton, Ph.D., an associate professor of neurology and psychiatry, both at the University of Pittsburgh.

"The good news is it appears the brain can tolerate these plaques for years before the effects are apparent," Klunk said. "The bad news is that by the time the symptoms emerge, the disease has had perhaps a 10-year head start."

Klunk and colleagues suspect that people with amyloid deposits and normal brain functioning have a high risk for the future development of Alzheimer's disease in the future. Definitive evidence demonstrating this hypothesis has yet to be collected, however.

"We simply do not yet know what a positive PIB scan means in a normal individual," Klunk said.

University of Pittsburgh researchers plan to track the study subjects over time to more fully understand how the presence of amyloid deposits translates into future risk for Alzheimer's disease.