Marc Diamond, M.D., is a native of Berkeley, California. He graduated from Princeton University in 1987 with an A.B. in History. He entered the UCSF School of Medicine in 1987, and he carried out research on transcriptional regulation by the glucocorticoid receptor for two years with Keith Yamamoto, Ph.D. as a Howard Hughes Medical Student Research Fellow. Dr. Diamond received his M.D. from UCSF in 1993 where he also completed an internship, residency, and chief residency in Neurology in 1997. He completed a postdoctoral fellowship in the laboratory of Dr. Yamamoto until 2001, working on two polyglutamine diseases—spinobulbar muscular atrophy and Huntington’s disease.
Dr. Diamond joined the faculty of the Department of Neurology at UCSF from 2002-2009, before moving to Washington University in St. Louis in 2009, as the David Clayson Professor of Neurology. He joined the faculty of UT Southwestern Medical Center in 2014 as the founding director of the Center for Alzheimer’s and Neurodegenerative Diseases. He is interested in neurodegenerative diseases linked to protein aggregation, and the role of prion mechanisms in the normal and abnormal physiology of protein amyloids.
We are studying neurodegeneration from the standpoint of proteins that adopt a self-replicating pathological conformation. All major neurodegenerative diseases are relentlessly progressive, and virtually all are linked to the accumulation of protein amyloids, which are ordered, paracrystalline assemblies that typically are rich in beta sheet structure. Over 10 years ago we wondered why neurodegenerative diseases feature pathology that spreads through the brain. We hypothesized that prion mechanisms could explain myriad features of common diseases such as the tauopathies and synucleinopathies: the accumulation of intracellular amyloids; progression through neural networks and connected cells; and phenotypic diversity. The basic biology of prions, infectious proteins that replicate distinct pathological structures and cause distinct patterns of neuropathology, serves as a model that provides new ideas about the basis of neurodegeneration in common disorders.
The human prion protein (PrP) causes neurodegeneration based on trans-cellular propagation of pathology. Pathology begins with a “seed” that can arise spontaneously within the brain, or, much more rarely, can be introduced by environmental exposure, i.e. infection. The seed acts as a template to convert normal PrP to a new structure that causes disease, and can spread pathology throughout the brain. We have discovered that the tau protein, which accumulates in intracellular and extracellular amyloids in a variety of neurodegenerative diseases, has essential characteristics of PrP. This can explain the relentless progression and phenotypic diversity of the myriad disorders termed “tauopathies,” which include Alzheimer's disease, the frontotemporal dementias, and chronic traumatic encephalopathy. The same principles apply to other disease-causing proteins that form amyloid structures, such as α-synuclein.