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January 22, 2004

New compound may lead to Alzheimer’s breakthrough

Pitt scientists in collaboration with researchers at Sweden’s Uppsala University have laid the groundwork for a new era in Alzheimer’s disease research by completing the first human study of a compound that, through positron emission tomography, enables them to peer into the brains of people with the memory-stealing illness and see the telltale plaque deposits they believe are at the root of the disease.

Alzheimer’s is a debilitating brain disease that affects memory and cognitive function in approximately 4 million Americans today and, if unchecked, will strike as many as 14 million during the next 50 years. The distinguishing factor between Alzheimer’s and other dementias is the formation of a protein substance called beta-amyloid, or amyloid plaque, that is believed to contribute to the death of brain cells. Results of the study were chosen for rapid publication online in the early view section of Annals of Neurology.

According to the researchers, creation of the compound, dubbed Pittsburgh Compound B (PIB), is a significant development that may provide long-sought answers to questions of how the disease begins and grows, as well as contribute to a better understanding of how effective new drug therapies are at preventing, delaying or treating Alzheimer’s. “PIB has given us a new tool to view the amount of amyloid in the brains of living Alzheimer’s disease patients,” said William E. Klunk, associate professor of psychiatry at Pitt’s School of Medicine and co-inventor of PIB. “Using PIB, we will likely be able to follow the progression of the disease and speed the development of promising new therapies aimed at halting the build-up of amyloid in the brain.” Alzheimer’s disease, like stroke, is a significant cause of dementia in people over the age of 65. But unlike stroke, which begins with a single event, there is no way for doctors to pinpoint when the brains of people with Alzheimer’s begin to change, and this lack of knowledge is a real detriment when it comes to creating and testing therapies to prevent the illness.

The plaque deposits form in areas of the brain where memory and cognitive functions are carried out, while leaving areas responsible for motor functions alone. This means a person with Alzheimer’s can be cognitively helpless while being physically robust. Actual visual inspection of amyloid in the brain has been the only way to make a definitive diagnosis of Alzheimer’s, and previously could only be done at autopsy. Chester A. Mathis, a Pitt professor of radiology and co-inventor of PIB, said: “The ability to detect and quantify amyloid in the brain has the potential to impact several areas of Alzheimer’s research, including the assessment of anti-amyloid treatments under development by many major pharmaceutical companies. PIB may allow us to study the very roots of Alzheimer’s by assessing the extent of amyloid deposition in people years before Alzheimer’s symptoms appear.”

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