Gang Tong, M.D., Ph.D.
University of California at San Diego
La Jolla, California

2003 New Investigator Research Grant

Many scientists believe that the prime suspect in Alzheimer’s disease is beta-amyloid, a protein fragment clipped from its parent molecule amyloid precursor protein (APP). Beta-amyloid eventually aggregates into the plaques that are a hallmark Alzheimer brain abnormality. A growing body of evidence suggests that the most damaging form of beta-amyloid is not the plaques themselves but its preliminary stages of aggregation.

This project will study postmortem samples of Alzheimer brain tissue and cultured rat brain cells to explore the effect of beta-amyloid oligomers, a stage in which a few strands of beta-amyloid clump together. The researchers will focus on oligomers’ impact on synapses, microscopic junctions across which nerve cells share information in the form of chemical and electrical signals. Patterns of synaptic connections and the varying strength of the electric signals transmitted across them form the basis of learning and memory. The team believes that beta-amyloid oligomers may damage existing synapses and hamper nerve cell’s ability to form new ones. Both effects could disrupt formation and retrieval of memories as well as lead to nerve cell death. This project may provide better understanding of the mechanisms underlying synapse loss in the Alzheimer brain and suggest strategies to prevent it.