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Pittsburgh at the Forefront of The Brain Revolution

Alzheimer’s disease is the most expensive ailment to treat and the sixth-leading cause of death in the United States. Pittsburgh has become a battleground in the fight against the devastating illness, thanks to the decade-long quest of two Pittsburgh researchers whose work is on track to change the face of medicine and affect millions worldwide.



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Dr. Oscar Lopez, a Pitt neurologist, heads a project in partnership with the University of Chile that is focused on developing a blood test that checks for abnormal levels of tau protein, which could help to diagnose and treat Alzheimer’s disease.
 

The road ahead

With clinical trials well underway through the DIAN study, Klunk and his colleagues are looking ahead to the next steps in the quest for a viable treatment.
Mathis continues to develop radiotracers at Pitt, this time focusing on tau, the other protein thought to cause Alzheimer’s. Various forms of tau are implicated in several brain diseases, including frontotemporal dementia and chronic traumatic encephalopathy. Compared to tau, finding a tracer that worked with amyloid “was relatively easy,” Mathis says. Tau is a more difficult target.

​Klunk is focusing on another population whose genetics dramatically impact their chances of developing Alzheimer’s: people with Down syndrome. If they reach the age of 60, anywhere from half to 80 percent of people affected by Down syndrome develop Alzheimer’s because the extra chromosome they carry — 21 — also is responsible for the body’s production of amyloid, so they make 50 percent more of the protein than the rest of the population.

“It’s the most well-defined genetic form of Alzheimer’s disease,” says Klunk.

Pitt has been testing a small group of about 40 subjects since June 2016, using the same protocol developed for the autosomal dominant patients, including the DeMoes. The eventual goal is to get those subjects to clinical treatment trials such as the ones the families with mutations are in.

“These are young folks who don’t have the other neurodegenerative pathologies,” says Klunk. “They’re a group that justifies themselves.”

Klunk and Mathis continue to go on fly-fishing expeditions, and they’ve relaxed the no-shop-talk rule somewhat. Now, though, they’re talking about where they’ll fish in their retirement.

Another important project, headed by Pitt neurologist Dr. Oscar Lopez in partnership with the University of Chile, focuses on developing a blood test that checks for abnormal tau levels, helping to diagnose members of the general population.

“All these are pieces of a big puzzle,” Lopez says. “In the future … if we have a preventive treatment, we’ll be able to determine the timing of the treatment.”

In 2013, G8 nations participating in an international summit on dementia set an ambitious goal: Find a viable treatment for Alzheimer’s disease by 2025. It was the first G8 summit on a disease since HIV and AIDS, and it represented a call to action, including funding for research.

Klunk says the effect of increased funding “has certainly been palpable,” and he, like many other researchers, remains hopeful — though they always worry about funding cuts. After all, he knows something about maintaining optimism after years of failure: he’s been there and done that.

Contemplating the work that led him and Mathis to discover PiB, Klunk said once: “You’ve got to fail to understand and proceed.”

Mathis puts it more bluntly: “Bill always says we got really lucky,” he muses. “I say, ‘No, Bill, we didn’t get lucky. We were due success. A blind squirrel does find a nut once in awhile.’”

On Valentine’s Day in February, Mathis turned to his wife and said: “Do you know what happened today, 15 years ago?”

She didn’t, so he reminded her: The first human being was dosed with PiB. Time hasn’t dimmed the satisfaction in his voice:

“That was a very sweet day.”  

Niki Kapsambelis is a freelance journalist who lives in Mt. Lebanon and a previous contributor to Pittsburgh Magazine. Her work also has appeared in publications around the world, including the Washington Post, Los Angeles Times, People and the Associated Press. “The Inheritance” is her first book.
 

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