Imaging Compound IDs Telltale Signs of Alzheimer's

Finding could lead to better diagnosis, treatments, experts say

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By
HealthDay Reporter

TUESDAY, March 13, 2007 (HealthDay News) -- Scientists have confirmed that an imaging agent known as Pittsburgh Compound B binds to abnormal protein growth in the brain that are a signature of Alzheimer's disease.

The results hold a two-fold promise, both for being able to better diagnose the disease and for being able to judge the effectiveness of drugs that target the amyloid beta protein.

"This study confirms the accuracy of the new PiB [Pittsburgh Compound B] molecular imaging for amyloid," said Dr. John Growdon, senior author of the paper and director of the Memory Disorders Unit at Massachusetts General Hospital in Boston. "It indicates that PiB uptake does not necessarily indicate Alzheimer's disease. It does, however, indicate that this would be a good biological marker or surrogate outcome measure in drug trials directed toward clearing or reducing the amount of amyloid in the brain."

Maria Carrillo, director of medical and scientific relations at the Alzheimer's Association, added: "We are pretty excited about seeing this research come out. PiB does indeed show great promise and it shows promise in two different arenas, diagnosis and monitoring anti-amyloid therapies, which are potentially just around the corner."

If one application doesn't work, the other one still could, Carrillo added.

According to the Alzheimer's Association, about 4.5 million Americans have the disease, a number that has more than doubled since 1980. Many more suffer from cognitive impairment, which could be a harbinger of the disease. And scientists project that some 13.2 million older Americans will have Alzheimer's disease by 2050, unless new ways are found to prevent or treat the disease.

Diagnosis of Alzheimer's is a notoriously tricky affair, and is never 100 percent definite until an autopsy is performed.

Many experts believe that Alzheimer's is caused by a build-up of amyloid plaque proteins in the brain. But, again, the protein can only be detected through an autopsy.

Previous studies have shown that PiB, a compound invented by researchers at the University of Pittsburgh Medical Center, binds to amyloid-beta in the brains of mice and also shows up on PET scans of human patients who are thought to have Alzheimer's.

PiB crosses the blood-brain barrier, giving a strong PET signal in the cortex of brains of people with suspected Alzheimer's. But there had been no confirmation that PiB was actually lighting up amyloid-beta deposits.

The new study, carried out by researchers at Massachusetts General Hospital and published in the March issue of Archives of Neurology, involved the case of a 76-year-old man with memory loss. He was eventually diagnosed with dementia with Lewy bodies, which does not also preclude the presence of Alzheimer's.

While he was still alive, the man enrolled in a study involving PiB imaging and, as part of that study, underwent a standard positron emission tomographic (PET) bran scan that suggested Alzheimer's. The scan showed that PiB had been taken up throughout the cerebral cortex, the outer layer of the brain.

Three months later, the man died following a head injury and an autopsy was performed.

The man did indeed have dementia with Lewy bodies as well as several features characteristic of Alzheimer's. Most of the amyloid beta was found in the walls of blood vessels, a condition known as cerebral amyloid angiopathy.

The distribution of the plaques matched the distribution seen in the PiB study, the authors stated. The man had features of Alzheimer's, but not at a level that indicated a true diagnosis of the disease.

While the absorption of PiB does indicate the presence of amyloid in the brain, a positive PiB PET scan does still not mean a definite diagnosis of Alzheimer's. About 15 percent of people in previous PiB studies with no cognitive impairment had some level of PiB uptake, the authors stated.

"PiB is going to be pivotal for this decade," Carrillo said. "But we need more studies like this. It's not enough on its own."

The Alzheimer's Association last year awarded its largest research grant to the Alzheimer's Disease Neuroimaging Initiative (ADNI) to expand the study to include PET scans using PiB. This and another grant to the ADNI marked the association's single largest investment ever in a research project.

"We decided that because this had so much potential, it was important that it be studied on the clinical trial level," Carrillo explained. "Hopefully after three years of following the same people we will have a much more definitive idea of what types of diagnosis could be made with PiB and how we can actually help in monitoring anti-amyloid therapies that could be out this year if we're lucky. This is just the tip of the iceberg."

More information

Visit the Alzheimer's Association for more on this disease.

SOURCES: John Growdon, M.D., director of the Memory Disorders Unit, Massachusetts General Hospital, Boston; Maria Carrillo, Ph.D., director, medical and scientific relations, Alzheimer's Association, Chicago; March 2007, Archives of Neurology

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