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Trying to Stop a Tsunami

BU’s Alzheimer’s Disease Center: working to diagnose, treat, cure

| From BU Today | By Barbara Moran

Robert Stern is director of the clinical core of the BU Alzheimer’s Disease Center. Photo by Vernon Doucette

The statistics on Alzheimer’s disease are grim. According to the Alzheimer’s Association, one in eight older Americans has the disease, adding up to 5.4 million people in the United States alone. As the population ages, these numbers are expected to grow (some estimates project the number at more than 15 million by 2050), leading experts to warn of an oncoming “Alzheimer’s tsunami,” which could decimate countless families and overburden the health care system.

But perhaps the worst thing about Alzheimer’s is that it has no cure, leading some to say that a diagnosis of the disease is worse than being told you have cancer. Although it is the sixth-leading cause of death in the United States, Alzheimer’s disease is the only one among the top 10 that cannot be prevented, cured, or even slowed.

“We’ve been studying Alzheimer’s disease for 100 years, and we still don’t know how to cure it, treat it, or diagnose it,” says Robert Stern, a School of Medicine professor of neurology and neurosurgery and director of the clinical core of the BU Alzheimer’s Disease Center (ADC), one of 29 federally funded Alzheimer’s disease centers nationwide. Yet, says Stern, who is also a codirector of BU’s Center for the Study of Traumatic Encephalopathy, for the first time in decades there is hope on the horizon, both for treating this deadly disease and for catching it early.

Why has Alzheimer’s proven so hard to treat? After all, look at AIDS. A diagnosis of AIDS was a death sentence 20 years ago. Now, with testing and treatment, doctors view AIDS as a serious but manageable chronic condition. Why not Alzheimer’s? “AIDS isn’t as complicated as Alzheimer’s,” says Stern. “We know exactly what causes AIDS—it’s a virus. There isn’t a single virus or bacteria or genetic mutation we know of yet that causes routine Alzheimer’s. It’s a multifaceted mechanism that leads to neurodegeneration.”

Alzheimer’s is a disease that attacks the brain, causing problems with memory, thinking, and behavior. Symptoms usually develop slowly and get worse over time, eventually making daily tasks impossible. Although scientists don’t know the cause, they can recognize a brain with Alzheimer’s when they see one: it’s riddled with twisted strands of the protein tau (tangles) and fragments of a protein called beta-amyloid (plaques). There’s also telltale nerve damage and tissue death in the brain.

Unfortunately, until very recently the only way to definitively diagnose Alzheimer’s was through an autopsy. The best doctors could do for living patients was diagnose “probable Alzheimer’s disease,” based on clinical examination. At the ADC, says Stern, “we’re really darn good at diagnosing Alzheimer’s disease,” getting it right about 94 percent of the time. But regular clinicians don’t do as well, because they don’t specialize in this disease and don’t see cases every day. As a result, people are not diagnosed as often as they should be. Sometimes, says Stern, clinicians avoid diagnosing a patient with Alzheimer’s because they aren’t sure of the diagnosis or simply because there’s no good treatment. So their view is, why traumatize the patient and family?

Like Sisyphus

But in 2011 the Alzheimer’s Association and the National Institute on Aging released new diagnostic criteria for the first time in 40 years. In addition to the standard cognitive tests and clinical examination, doctors and researchers can now look for specific biomarkers: elevated tau and low amyloid in the spinal fluid, atrophy in specific parts of the brain like the hippocampus, and special PET (positron emission tomography) scans that can measure excess amyloid in certain parts of the brain. “Now there are objective, highly accurate methods of diagnosing someone with Alzheimer’s before they even have any symptoms,” says Stern. “This is extremely important, because if we had drugs that could change the course of the disease, they would work better if we gave them earlier.”

The problem is, of course, that there are no good drugs to treat the disease. The U.S. Food and Drug Administration (FDA) has approved two types of drugs—cholinesterase inhibitors and memantine—that help regulate certain neurotransmitters important for learning and memory and may help lessen the symptoms of Alzheimer’s. However, the drugs don’t work very well. They don’t slow the progression of the disease, but only temporarily relieve symptoms, and that only in some people. “These only help if there are enough cells working,” says Stern. “Like Sisyphus, you keep pushing the rock, but you’re not getting anywhere because brain cells keep dying.” Because the payoff is so small, he says, these drugs are not even approved for use in Europe.

Scientists are now researching new drugs to attack different aspects of the disease: drugs to lower amyloid production, remove excess amyloid from the brain, reduce tau aggregation, or reduce inflammation. Stern notes that there are 150 clinical trials for new Alzheimer’s drugs under way, and most of them target amyloid. But, he says, coming up with a bulls-eye drug therapy is tricky, since brain chemistry is complicated. Amyloid, for instance, is like cholesterol, in that not all types are harmful. The problem comes when a person has a lopsided ratio of bad amyloid to good. “But the good amyloid does a lot of important stuff,” Stern says. “You can’t just reduce all the amyloid in the body without causing harm.”

And, he says, there’s another issue with targeting amyloid. Many scientists believe that excess amyloid appears at the early stages of Alzheimer’s disease, before people even show any symptoms. “If amyloid is the beginning of the cascade and right now you can only target treatments once people are symptomatic with the disease,” says Stern, “it may be too little too late.”

That’s why, for Stern, the key is not just new drugs, but early diagnosis. “Eventually we will have Alzheimer’s screening,” just like we have screening for breast, colon, and prostate cancer, he says. “If we could diagnose the disease much earlier, we could alter the course enough so that clinical dementia would never be observed.”

His group is now starting a clinical trial of bapineuzumab, an antibody that may increase the clearance of beta-amyloid from the brain, on people with mild cognitive impairment who have the biomarkers for probable Alzheimer’s disease. While he is hopeful that bapineuzumab will have an effect, ultimately he thinks that treatment will come from a host of drugs. “I don’t see there being one best treatment,” he says. “There will be a cocktail of things to be used depending on genetics and the stage of the disease. It’s such a complex disease that no one drug will work for everyone.

“But there is definitely reason for hope. There will be effective treatments for Alzheimer’s,” Stern says. “Very soon.”

Barbara Moran (COM’96) is a science writer in Brookline, Mass. She can be reached through her website WrittenByBarbaraMoran.com.

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