Scott A. Small, M.D.
Boris and Rose Katz Professor of Neurology
Division of Aging and Dementia
Director, Alzheimer's Disease Research Center
Taub Institute for Research on Alzheimer's Disease and the Aging Brain
After graduating from NYU with a B.A. in experimental psychology, Dr. Small began the MD/PhD program at Columbia University in Eric Kandel’s laboratory. Discovering that he enjoyed patient care more than he anticipated, he decided to focus exclusively on his medical training. After completing a medical internship at UCLA, a neurology residency and chief residency at Columbia, and a fellowship with Richard Mayeux, Dr. Small "returned" to research. Informed by his prior experience studying the psychology of memory, the physiology of neurons, and the neurology of the disease he began a research program at Columbia dedicated to investigating intractable disorders of the brain. Taking a decidedly top-down approach, he pioneered the development of brain imaging tools designed to pinpoint brain dysfunction in human patients and mouse models of disease. More recently, Dr. Small has combined brain imaging with gene-expression technologies to uncover novel molecular defects underlying Alzheimer’s disease and aging.
Dr. Small is the recipient of numerous awards, including the Beeson Scholar Award in Aging Research from the American Federation on Aging, the McKnight Neuroscience of Brain Disorders Award, the Derek Denny-Brown Young Neurological Scholar Award from the American Neurological Association, and the Lamport Award for Excellence in Clinical Science Research from Columbia University.
A ‘neuronal population’ is defined as a cluster of neurons that are unified in their molecular expression profiles. The brain is made of thousands of neuronal populations, and each disorder of the brain differentially targets a specific neuronal population. Dr. Small’s lab has been guided by this basic clinical principle, with the belief that in order to understand, diagnose, and ultimately treat any brain disorder the most vulnerable neuronal population needs first to be pinpointed. By improving spatial resolution, Dr. Small’s lab has adapted fMRI (functional magnetic resonance imaging) so that dysfunction in small subregions of the brain can be visualized in living subjects. In so doing, the lab has pinpointed the neuronal populations within the hippocampal formation most vulnerable to normal aging, and has contrasted this anatomical pattern to the earliest stages of Alzheimer’s disease. These findings suggest a way to diagnose Alzheimer’s diseases as early as possible, before the onset dementia. Why should one neuronal population be vulnerable to normal aging while another is vulnerable to Alzheimer’s disease? In order to answer this question, the lab has combined fMRI with microarray, and has begun isolating rogue molecules that cause age-related memory decline versus those that contribute to Alzheimer’s disease. This cellular and molecular information will clarify basic mechanisms of brain dysfunction, and hopefully will lead to novel avenues of treatment.