The Quest for an Alzheimer’s Cure: An Interview with Dr. Paul Coleman

Dr. Paul Coleman

For 7-year-old Paul David Coleman, the backyard pond was a source of endless fascination — and ultimately would be the place that ushered him into the world of science and single-cell research.

“There was a pond in the woods back of the house where my parents had a summer place in Connecticut. I would catch tadpoles and dissect frogs to see how they were inside,” he says. Today, at age 86, with a Ph.D. in physiology and psychology from the University of Rochester and a National Institutes of Health fellowship from Johns Hopkins School of Medicine, Coleman hasn’t lost his fascination with slippery, slimy, squishy objects.

As senior scientist and director of the L.J. Roberts Center for Alzheimer’s Research at Banner Sun Health Research Institute in Sun City, Arizona, Coleman has seen his backyard grow into a much bigger pond. The institute houses the world’s premier bank of human brains, which are harvested at high-speed precision from the 50 miles surrounding the center, where the median age is 75.

Rows of heavily monitored freezers line the walls of the research institute, packed with Tupperware containers by the thousands that store high-quality brain tissue. These containers hold out a mighty hope that scientists will soon have the answers to diagnose and treat one of humanity’s most dark and elusive diseases — Alzheimer’s.

From the moment Jim Eberwine, Ph.D., handed him a rat’s hippocampus during a Cold Springs Harbor Laboratory course on cloning neural genes, Coleman’s passion for unlocking the mysteries of single cells in animal and human brains hasn’t wavered. When his instructor directed him to report back on the gene expression in a block of tissue that contained huge numbers of different cells, Coleman was nonplused. “The idea of grinding up a block of tissue violated my every aesthetic sense, and it made no scientific sense to me to ‘homogenize’ so many distinctive cells — some of which could be healthy and others diseased,” he explains.

One thing led to another, and before long Coleman and his professor had developed a new method for isolating single neurons to study gene expression. Coleman’s next step was to apply
the technique to human brains. But he didn’t stop there. Today, the technique he and his team mastered enables researchers to analyze the activity of as many as 20,000 genes within a single cell. As Coleman peeled away the layers of mystery surrounding how genes worked, he became increasingly fascinated with epigenetics — the study of how a person’s genetic code can be altered by the environment; more specifically, how DNA, genes, gene functioning, and genetic vulnerabilities are connected to Alzheimer’s disease.

The man who admits to having failed his Quaker kindergarten is today arguably one of the world’s top Alzheimer’s researchers and — true to his convention-shattering discovery in 1979 that revealed that the brain does not stop developing with age — shows no sign of slowing down.

In fact, it appears that Coleman’s career launched like a rocket ship after he turned 60. That’s when he became editor-in-chief of the journal Neurobiology of Aging; was named as one of an elite few to receive the National Institutes of Health Leadership and Excellence in Alzheimer’s Disease research award; and received a $1-million boost for his work from the Alzheimer’s Association as part of the Pioneer Award for Alzheimer’s Disease Research. He is also listed among about 100 researchers and other advocates as a leading supporter of “The National Alzheimer’s Strategic Plan: A Report of the Alzheimer’s Study Group,” co-chaired by Senators Newt Gingrich and Bob Kerrey, and issued as a call to action in 2009.

It was during his seventh decade that Coleman developed a blood test that is able to predict a future diagnosis of Alzheimer’s — as he says, “not perfectly but better than chance.” The test must undergo replication, clinical trials, and FDA approval before it can be made available to doctors and their patients. Currently, Coleman is working with a company that may be able to create a process that makes the test accessible and affordable — about $30 to $40. Unfortunately, funding from the NIH is no longer available to advance this work.

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