William Klein Professor

Research Summary

Cell and structural biology of Alzheimer’s disease; memory-linked synapse structure and signal transduction

We have discovered novel neurotoxins that appear to account for memory failure in Alzheimer’s disease. We call these molecules “ADDLs,” and they comprise small soluble oligomers of the amyloid _ peptide. ADDLs target memory-linked synapses and interfere with mechanisms essential for memory formation. We do not know how this happens at the molecular level, but current experiments are designed to discover specific ADDL toxin receptors and elucidate how these toxin receptors disrupt memory-linked synaptic structure and signaling. Structural studies of ADDLs, which are tremendously elevated in AD-afflicted brain, should play an important role in developing the first effective therapeutic Alzheimer’s drugs and vaccines. Discovering how ADDLs disrupt memory formation ultimately may give new insight into molecular memory mechanisms as well as the brain’s potential for memory enhancement.

Selected Publications