Molecular Imaging Sheds New Light On Progression Of Alzheimer’s Disease

The groundbreaking discovery by University of Pittsburgh researchers Chester Mathis, PhD, and William Klunk, MD, PhD, is being watched with great interest.

Pittsburgh Compound B (PIB) binds to the abnormal amyloid plaque in the brain. When imaged with a PET scan, PIB shows researchers actual pathological changes in the brain that could turn out to be the best and earliest signs of the disease.

Pittsburgh at the forefront of Alzheimer’s research

Researchers at the University of Pittsburgh Medical Center (UPMC) are revolutionizing the fight against Alzheimer’s disease (AD). Scientists and researchers at the University of Pittsburgh recently discovered a new agent, dubbed “Pittsburgh Compound B,” which allows researchers to visualize for the first time in living people the brain plaque suspected of causing the memory-stealing disease. Previously, the presence of plaque could be confirmed only during autopsy.

Pittsburgh Compound B (PIB) binds to the abnormal amyloid plaque in the brain. When imaged with a PET scan, PIB shows researchers actual pathological changes in the brain that could turn out to be the best and earliest signs of the disease. It may be possible that these changes could be detected as many as 10 years before patients experience serious memory loss.

The groundbreaking discovery by University of Pittsburgh researchers Chester Mathis, PhD, and William Klunk, MD, PhD, is being watched with great interest. Along with Drs. Klunk and Mathis, researchers like Steven DeKosky, MD, director of the Alzheimer Disease Research Center at UPMC, are currently collaborating with investigators around the world to further study PIB and other compounds, as well as potential new treatments for Alzheimer’s.

Pittsburgh Compound B was developed after more than a decade of work by University Drs. Klunk and Mathis. Dr. Klunk is an associate professor of psychiatry who studies Alzheimer’s disease, while Dr. Mathis specializes in developing radiopharmaceuticals — compounds that are injected into the body and temporarily emit radioactive particles that can be captured by PET imaging to reveal anatomical clues.

Working with three classes of dyes used to detect plaque in the lab, Drs. Klunk and Mathis worked for years testing hundreds of compounds before developing PIB.

“This is in the early stages of development,” says Dr. DeKosky. “But if our success continues, it’s possible there could be a commercially available product for the early diagnosis of Alzheimer’s within the next decade.”

Using PIB, doctors may someday be able to follow the progression of the disease and identify people who are at increased risk for AD long before any symptoms occur.

“Until the development of Pittsburgh Compound B, there was no way to measure a decrease in AD plaque or possible remission of the disease,” says Dr. DeKosky. “What makes PIB remarkable is that, for the first time, doctors may be able to tell definitively if treatment is working.” Dr. DeKosky says before this discovery by Drs. Mathis and Klunk, no one was able to develop a tracer that binds to the specific abnormal protein in AD. All of the other imaging studies simply show shrinkage in parts of the brain or brain activity changes in different regions.

“For the last 20 years, we’ve talked about finding a noninvasive way to make a definite and specific diagnosis and being able to quantify the amount of plaque in the brains of people who have AD,” says Dr. DeKosky. “If we can make a specific diagnosis through imaging, then we can track the effectiveness of new drugs and other treatments. There is nothing out there right now anywhere near as direct, that can tell us definitively whether or not a drug reaction and response helps the disease.”

Furthermore, use of the compound may also tell researchers whether the hypotheses upon which therapies are being developed are correct. “That’s important, as is identifying early-stage patients before it’s too late,” says Dr. DeKosky.

“The future is very exciting, and it’s satisfying to know that we were at the forefront of advancing the science,” says Dr. Mathis. “Right now we’re setting the stage to use Pittsburgh Compound B in collaboration with a number of companies that are trying to target therapies for AD. If these therapies do what we hope they will do, then it will become more important to determine if a person has AD at an earlier stage.”

Dr. Mathis says another very important goal will be to nail down amyloid plaque’s exact role in Alzheimer’s disease. While most doctors suspect that it causes Alzheimer’s, there isn’t yet 100 percent agreement on the theory. If amyloid plaque turns out not to be a central cause, Dr. Mathis says, such a finding could completely redirect research.

Finally, PIB and improved radiotracers now under development at the University of Pittsburgh will allow researchers to follow amyloid deposits in Alzheimer’s patients and older people without the disease, helping to better define the normal aging process in the brain.

Alzheimer’s is a very complex disease, one that is just beginning to be understood. It steals the mind and memory. It devastates families and makes strangers out of life-long partners. Approximately 4 million Americans have Alzheimer’s, and if left unchecked, it will strike as many as 14 million during the next 50 years. UPMC’s new research may stem the advance of this debilitating disease.

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Scientists find early signs of Alzheimer’s

“We found the earliest predictor,” said the lead researcher, Lisa Mosconi of New York University School of Medicine. “The hippocampus seems to be the very first region to be affected.”

Source USA Today

A subtle change in a memory-making brain region seems to predict who will get Alzheimer’s disease nine years before symptoms appear, scientists reported Sunday.
The finding is part of a wave of research aimed at early detection of the deadly dementia — and one day perhaps even preventing it. (Related: Lifestyle, Alzheimer’s link strengthen Disease explained)

Researchers scanned the brains of middle-aged and older people while they were still healthy. They discovered that lower energy usage in a part of the brain called the hippocampus correctly signaled who would get Alzheimer’s or a related memory impairment 85% of the time.

“We found the earliest predictor,” said the lead researcher, Lisa Mosconi of New York University School of Medicine. “The hippocampus seems to be the very first region to be affected.”

But it is too soon to offer Alzheimer’s-predicting PET scans. The discovery must be confirmed. Also, there are serious ethical questions about how soon people should know that Alzheimer’s is approaching when nothing yet can be done to forestall the disease.

Still, the discovery may provide leads to scientists searching for therapies to at least delay the onset of the degenerative brain disease. It already affects 4.5 million people in the U.S. and is predicted to strike 14 million by 2050 as the population ages.

Moreover, researchers are honing in on lifestyle choices that may help protect the brain in the first place.

“It’s exciting that we can even talk about prevention,” said William Thies, scientific director of the Alzheimer’s Association. He noted that just 10 years ago there was hardly any research into that possibility.

Among the findings presented Sunday at the association’s first Alzheimer’s prevention conference:

•People who drink fruit or vegetable juice at least three times a week seem four times less likely to develop Alzheimer’s than nonjuice drinkers, according to a study of 1,800 elderly Japanese-Americans. The theory is that juice contains high levels of polyphenols, compounds that may play a brain-protective role.

•Less education, gum disease early in life, or a stroke were more important than genes in determining who got dementia, concluded a study of 100 dementia patients with healthy identical twins. Education stimulates neuronal growth; gum disease is a marker of brain-harming inflammation.

•Decreasing social activity in old age is a risk factor, a National Institute on Aging study suggests. It is not clear if the men in the study became less social because Alzheimer’s already was at work, but social activity is mentally stimulating.

A brain-healthy lifestyle aside, a big quest is to develop ways to identify Alzheimer’s disease before symptoms emerge — finding biomarkers that could be targets for preventive therapies.

Think of it as hunting the equivalent of the cholesterol test for Alzheimer’s, Dr. Neill Graff-Radford of the Mayo Clinic said.

He measured blood levels of different types of beta amyloid, the sticky protein that makes up Alzheimer’s hallmark brain plaques, in 565 people. Those with lowest ratios of a particular amyloid type were three times more likely to develop dementia within five years.

The reason: Probably less amyloid was floating in the blood because it was sticking in the brain instead.

PET scans already can show Alzheimer’s plaques in advanced disease. Mosconi’s study is the first to so rigorously examine people’s brains before symptoms appear.

PET, or positron emission tomography, scans show images of how brains use glucose, or sugar, which is the brain’s main fuel.

Mosconi scanned 53 healthy people. She tracked them for up to 24 years. Six so far have developed Alzheimer’s and 19 developed an Alzheimer’s precursor called “mild cognitive impairment,” or MCI. Those people showed less glucose metabolism in the hippocampus than the still healthy.

Other research supports the hippocampus’ early role.

University of Wisconsin researchers gave a different brain scan, called a functional MRI, to healthy adult children of Alzheimer’s patients. The researchers found that the hippocampus was not as active as in people without that familial risk.

To prove if these early indicators are real, the National Institute on Aging, with financial help from the pharmaceutical industry and Alzheimer’s Association, is beginning a $60 million study to scan the brains of 800 older Americans and try to pin down Alzheimer’s earliest biological changes.

That Alzheimer’s begins developing so early means even young people should adopt a brain-healthy lifestyle, said Dr. Mark Sager of the Wisconsin Registry for Alzheimer’s Prevention. “what we’re hoping is that 55 is not too late,” he said.

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