Holtzman is one of the leading experts in researching the underlying mechanisms that lead to Alzheimer's disease in an effort to improve diagnosis and treatment. In addition to seeing patients at the Alzheimer's Disease Research Center and the Memory Diagnostic Center, Holtzman leads a research team working with animal models of Alzheimer's. The group has been instrumental in showing how dangerous amounts of a protein fragment called amyloid beta begin to accumulate in the brain many years before symptoms arise. These basic science investigations have evolved over the years and are beginning to bridge the gap into the clinical arena.