CDR: Laboratory for Synapse Pathology
Director: Ottavio Arancio, M.D., Ph.D.

When a person develops a neurological disorder such as Alzheimer's disease (AD) or Parkinson's disease (PD), the brain cells begin to change the way they communicate. The Laboratory for Synapse Pathology wants to know what causes these long-lasting changes because they are thought to underlie the impairment of learning and memory. Functional communication between neurons occurs at specialized junctions called synapses. Combining cell biological methods with electrophysiological and behavioral techniques, researchers in Dr. Arancio's lab are exploring how a-synuclein, a protein involved in AD and PD, affects synaptic function. These techniques are also being used to examine how amyloid-b, the major component of the amyloid plaques in Alzheimer's disease, impairs nerve cell communication. Targets of amyloid-b action that are currently being investigated in the laboratory include co-factors enhancing amyloid-b toxicity. Some examples are the proteins known as receptor for advanced glycation endproducts (RAGE) and amyloid-b-binding-alcohol-dehydrogenase (ABAD). More recently, the laboratory has been exploring whether AD alters a cascade of proteins (guanylil-cyclase/cAMP-dependent-protein-kinase/CREB) that are important in normal learning and memory. These studies should lead to the design of novel therapeutic approaches that might be effective in preventing or delaying the onset of Alzheimer's disease and other neurodegenerative diseases.