Columbia University Medical Center

Alzheimer’s Disease Research Center: 25 Years of Insight With More Ahead

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Alzheimer’s researchers at Columbia, speaking at a panel in March, are cautiously optimistic that effective treatments for Alzheimer’s are on the horizon. “One has to feel that we’re at the cusp of real innovation and discovery and therapeutic intervention,” said Thomas Jessell, PhD, the Claire Tow Professor in the Departments of Neuroscience and Biochemistry & Molecular Biophysics. “But there are many, many mysteries left over.”

The panel discussion celebrated the 25th anniversary of the Alzheimer’s Disease Research Center at Columbia, currently directed by Scott Small, MD, the Boris and Rose Katz Professor of Neurology (in the Taub Institute, the Sergievsky Center, Radiology, and Psychiatry).

The Alzheimer’s Disease Research Center (ADRC) was created to “serve as a nucleus, an engine, a driver, a nerve center for the development of research programs on Alzheimer’s disease at Columbia,” said Richard Mayeux, MD, MSc, the Gertrude H. Sergievsky Professor of Neurology, Psychiatry, and Epidemiology. “We’ve grown into one of the top centers in the country.” An interdisciplinary initiative from its start, the ADRC has continued to support collaboration and serve as a hub for research, training, and outreach.

Columbia’s researchers have been trying to understand the genetic underpinnings of the disease, how the disease progresses, and how it can be stopped or delayed.

Recent findings about the way tau, the protein comprising the neurofibrillary tangles of Alzheimer’s, spreads through the brain of mice could open the door to treatment, said Karen Duff, PhD, professor of pathology & cell biology. “This is a radical new biology,” she said. “It opens up therapeutic opportunities, where now we have our protein of interest—our disease-causing protein—outside of the cell, able to be grabbed by biologics such as antibodies, which work much better outside of a cell than inside of a cell.”

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Speakers, from left: Scott Small, Richard Mayeux, Michael Shelanski, Thomas Jessell, Karen Duff, and Eric Kandel.

Similarly to Alzheimer’s, cognitive, or “normal,” aging is characterized by memory loss, but until recently “it was unclear whether this is an early phase of Alzheimer’s disease or an independent entity,” said Eric Kandel, MD, University Professor and the Kavli Professor. Investigators in the Kandel and Small labs then began to focus on this problem. Dr. Kandel’s lab found that mice show age-related memory loss even though they do not develop Alzheimer’s disease. Dr. Small’s team discovered that these two conditions appear in distinct parts of the brain. Collaborative investigations in the Kandel and Small labs found that a specific molecule, RbAp48, is associated with cognitive aging.

One has to feel that we’re at the cusp of real innovation and discovery and therapeutic intervention.                              –Thomas Jessell

Work by Dr. Small’s team and colleagues across the university also revealed a molecular link to Alzheimer’s disease. Focusing on the location and spread of neuronal sickness, they discovered that a protein complex called retromer is found in the affected areas. Retromer dysfunction has pathophysiological consequences and may have a role in multiple neurological disorders.

Work by Dr. Small’s team and colleagues across the university also revealed a molecular link to Alzheimer’s disease. Focusing on the location and spread of neuronal sickness, they discovered that a protein complex called retromer is found in the affected areas. Retromer dysfunction has pathophysiological consequences and may have a role in multiple neurological disorders.

Michael Shelanski, MD, PhD, the Henry Taub Professor of Alzheimer’s Disease and the Aging Brain (in Pathology & Cell Biology in the Taub Institute), studied the protein Ab, which makes up amyloid plaques, a main pathological feature of Alzheimer’s. Ab binds to nerve cells and causes downstream effects including memory deficits. “When you look just at a little pathway like this … you have an interesting microcosm of what really happens,” he said. The interactome—or the set of all interactions—in a neuron affected by Alzheimer’s has about 500,000 nodes, said Dr. Shelanski. “Every one of those steps in there is a potential target for a drug.”

Dr. Shelanski is confident that work at Columbia will play a crucial part in developing a therapy. “I am absolutely convinced that Columbia will lay the groundwork that leads to finding that drug, or that group of drugs,” he said.

A video of the full panel presentation can be viewed here.