NEW YORK – The first Stavros Niarchos Foundation Brain Insight Lecture of the new school year focused on Alzheimer’s Disease. The Mortimer B. Zuckerman Mind Brain Behavior Institute at Columbia University hosts the lecture series each year with the generous support of the Stavros Niarchos Foundation. Dr. Scott Small presented Understanding Alzheimer’s Disease Through Its Anatomical Vulnerability. The lecture was well-attended by Columbia students, faculty, scientists, and academics, as well as many community members interested in the research on the terrible, degenerative disease.

Dr. Small is the Director of the Alzheimer’s Disease Research Center at Columbia University, where he is the Boris and Rose Katz Professor of Neurology. He is appointed in the Departments of Neurology, Radiology, and Psychiatry.

With an expertise in Alzheimer’s disease and cognitive aging, Dr. Small’s research focuses on the hippocampus, a circuit in the brain targeted by these and other disorders, notably schizophrenia. He has pioneered the development and application of high-resolution functional MRI techniques that can pinpoint parts of the hippocampus most affected by aging and disease.

His lab then uses this information to try to identify causes of these disorders. Over the years, his lab has used this “top-down” approach to isolate pathogenic mechanisms related to Alzheimer’s disease, cognitive aging, and schizophrenia. More recently, his lab has used this insight for drug discovery and to develop novel therapeutic interventions, some of which are currently being tested in patients.

Dr. Michael Shadlen, Professor of Neuroscience, Principal Investigator at Columbia’s Zuckerman Institute, and Investigator at the Howard Hughes Medical Institute, gave the welcoming remarks and introduced Dr. Small, noting that we would hear a great deal about the hippocampus which is critical for memory.

The lecture began with a brief history of medicine from, of course, Greece and Hippocrates, the Father of Medicine, the belief that illness came from an imbalance in the humors, to the present with technology allowing doctors to see inside the human brain with MRI scans of remarkable detail.

Dr. Small spoke about the hippocampus, noting the diseases which affect it- Alzheimer’s Disease, cognitive aging, schizophrenia, post-traumatic stress disorder (PTSD), and depression, among others. Alzheimer’s begins in the hippocampus and then spreads to other parts of the brain, going through stages from cell sickness to cell death. “Spatial resolution matters in this work,” Dr. Small said of the type of cell blood volume (CBV) functional MRI used in the research. He explained that his team members, Frank Provenzano and Usman Khan, developed the algorithms, computer programs, to generate CBV maps of the Hippocampus of patients. The patterns show the difference between Alzheimer’s and cognitive aging which begin in completely different parts of the hippocampus.

Proteins are processed differently, and in the tiny area where there is more connectivity, more recycling, there is also more vulnerability, and the “endosomal traffic jams” that occur in Alzheimer’s disease could soon be regulated by medications targeting those vulnerable areas. Gene therapy, now being used much more, is also being developed as a way to treat Alzheimer’s.

Dr. Small mentioned the work of his colleague, Dr. Richard Mayeux, a noted geneticist, and that there is a strong case for a genetic cause since there are 20 genes linked to Alzheimer’s, and a genetic defect in endosomal trafficking could be a cause of the disease.

When asked if there is anything people can do to prevent Alzheimer’s, Dr. Small said the only thing he recommends, even to those diagnosed with the disease and in its early stages, is physical exercise which has been shown in studies to have positive effects on overall health and to delay the progression of the disease. Sleep deprivation, he added, may also trigger an increased risk for developing Alzheimer’s.

Slides highlighted Dr. Scott Small’s lecture on Alzheimer’s Disease in the Stavros Niarchos Foundation Brain Insight Lecture at Columbia University. Photo by Eleni Sakellis

The Stavros Niarchos Foundation Brain Insight Lecture at Columbia University focused on Alzheimer’s Disease. Photo by Eleni Sakellis