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A remarkable collection of Penn scientists, led by Virginia Lee and John Trojanowski, is attacking the merciless affliction known as Alzheimer’s, along with other neurodegenerative diseases. But the clock is ticking.


“Of all the things that can go wrong in aging,
the loss of the mind is far and away the worst and most feared.
And here, I believe, is the greatest of all opportunities for
medical science in the improvement of the human condition.”
—Lewis Thomas, The Fragile Species.


My mother’s dementia was inexorable and unyielding, my friend wrote. Her short-term memory went first while she retained her long-term memories. Then these, too, began to slip. She frequently talked about being with her mother, and I believe that she still had enough comprehension that she was looking for the comforting embrace of her mother to help her through her troubles. She came across as a scared little girl, and I couldn’t figure out how to provide that comfort for her.

As time went on, I would go to see her, and there would be no recognition of me on her part. She developed a 1,000-yard stare, focusing not on me but on some focal point far beyond me. Frequently during these stares, her eyes would come into focus on my features, and she would break down crying and give me a hug. It was as if she knew I was someone special to her, but she couldn’t define the relationship. Soon she would drift back into her own world, and eventually, she stopped recognizing me in any evident fashion. I came to expect that, although I held out hope that some day we could connect as mother and son and have one last meaningful conversation so that I could tell her I loved her, and to thank her for everything she did for me. That moment never came.

When the facility determined that she had reached a point where she had to move into the 24-hour-care wing, I consoled myself with the thought that she would not realize what was going on, and the transition would be relatively seamless. I was wrong, grossly and heartbreakingly wrong. As soon as I walked her over into the health-care wing, she immediately broke down crying and said, “I never thought it would come to this.”


Perhaps you know someone: a mother, a grandfather, a college friend, a spouse. If not, you will. Right now more than 5 million Americans have some level of Alzheimer’s disease, and the numbers are only going to get worse. On January 1 the first wave of baby boomers began hitting the beaches of old age. Behind them, the twilight flotillas stretch all the way to the horizon, waiting to discharge the next wave into the withering fire of dementia.

“We are beginning to enter a time where there’s going to be a huge escalation of Alzheimer’s patients,” John Trojanowski Res’80 is saying. “The baby boomers are entering the lifespan where every five years the incidence of Alzheimer’s will double.” There are 70 million baby boomers in the United States, he adds. Without a cure, “35 million will have Alzheimer’s by the time they reach 85.”

He pauses for a moment to let that sink in.

“We have the people,” he adds. “We have knowledgeable scientists. We have ideas. We have technologies. We have model systems. We have all the apparatus in place. We just need the resources to ramp up our efforts for drug discovery.”

Trojanowski (the William Paul Measey-Truman G. Schnabel Jr. Professor of Geriatric Medicine and Gerontology, and professor of pathology and laboratory medicine) is good at this big-picture stuff. He’s no slouch at the small-picture stuff, either, which goes down to the cellular level and beyond, to the very proteins and peptides of dementia. But when he plunks his lanky self into a chair in his modest office in the Maloney Building at HUP, affixes his large, deep-set eyes on his interlocutor, and starts talking, he’s a compelling speaker, segueing effortlessly and eloquently from one talking point to the next, answering questions before they’re even asked. Which is a good thing, since he’s become something of a spokesman on Alzheimer’s and other neurodegenerative diseases, and there’s a lot at stake.

Every now and then he tosses out a grandiose-sounding phrase like “a world without Alzheimer’s,” but he quickly brings himself back to reality—pointing out that cure, for example, is a relative term.

“A home run in my mind for an Alzheimer’s drug would be something that delays the onset of progression by as little as five years,” he says. “The economic modeling tells us that if we had a therapy that would slow progression by five years, within the next 40 or 50 years we would reduce the incidence of Alzheimer’s disease by 50 percent. So 50 percent fewer people get the disease because they die from something else.

“The average age of onset of Alzheimer’s is 73, 74 years old,” he adds. “So if you give people a pass on Alzheimer’s for another five years, then many will die of something else—a heart attack or what have you—but they won’t incur all the costs.”

We’re talking real money here, by the way. The Alzheimer’s Association estimates the annual cost of Alzheimer’s care in the US now at about $172 billion. Globally, the cost is about $604 billion, and by 2050, that number could rise as high as $3 trillion, Trojanowski says. A five-year delay could cut that number to around $1.5 trillion. “Half of $3 trillion is certainly a lot of money,” he adds. “But it’s far less than $3 trillion.”

Trojanowski is just one half of the remarkable husband-and-wife scientific team whose better if less grandiloquent half is Virginia M.-Y. Lee WG’84, director of the Center for Neurodegenerative Disease Research (CNDR), the John Ware 3rd Professor in Alzheimer’s Research, and professor of pathology and laboratory medicine. Having just finished an 80-minute interview with Lee, whose office is next door to Trojanowski’s in the Maloney Building, I’m frankly exhausted, though not unpleasantly so. Lean, petite, and practically crackling with energy, she has just brought me up to speed very fast and in minute detail on the small-picture side of their work—the intricate workings of the brain and its cells, the genetic mutations and misfolded proteins and destabilized microtubules, the efforts to find molecules that can cross the blood-brain barrier—as well as the deeply entwined fibrils of Penn’s neurodegenerative disease centers and programs.

Explaining that last part is no easy task. In addition to directing the very complex CNDR, Lee co-directs the Marian S. Ware Center for Alzheimer’s Drug Discovery Program, and has a firm hand in many other related ventures. Like Trojanowski, she is a highly productive and prolific researcher who, along with her colleagues, churns out dozens of influential papers each year. Two years ago she received the Alzheimer’s Association’s Khalid Iqbal Lifetime Achievement Award, and that’s only the most recent honor. For those who like metrics, Thomson Reuters Essential Science Indicators ranks her No. 6 in the world in the neuroscience and behavior category. Fourth on that list is Trojanowki, who is also co-director of the CNDR and of the Ware Program, and director of Penn’s Institute on Aging (IOA), its Alzheimer’s Disease Center, and its Udall Center for Parkinson’s Research.

The two are “at the forefront of the field of aging and dementia with their work on biomarkers and the role of tau [proteins] in neurodegenerative diseases,” says Ronald Petersen, director of the Mayo Clinic’s Alzheimer’s Disease Research Center and the man who treated former President Ronald Reagan. “They are not reluctant to pose bold and creative hypotheses that are intended to refocus our thinking on the underlying processes.”

Given the collaborative nature of their work, teasing out the threads of their individual efforts can be a challenge. Which doesn’t seem to bother either of them.

“John and I really work together in most things we do,” says Lee. “Our skill sets complement each other.” Or, as she put it in a recent video for Alzheimer’s Weekly: “In 1985, we decided to do a little experiment to see if we could collaborate and not kill each other.”

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COVER STORY: Untangling Alzheimer's By Samuel Hughes
Illustration by Anastasia Vasilakis

©2011 The Pennsylvania Gazette



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©2011 The Pennsylvania Gazette
Last modified 03/01/11