Rapid Effects of Soluble AB on Synaptic Structure

Project Summary

Barbara Calabrese, Ph.D. of the Scripps Research Institute, proposes studying in rat hippocampal neurons how the amyloid beta (ABeta) peptide, a key trigger of Alzheimer's disease pathology, induces early changes at synapses - the specialized connections between neurons that are essential for learning and memory. Research suggests that in early stages of Alzheimer's disease cognitive disruption reflects significant loss in the numbers and/or function of synapses. The soluble forms of ABeta have been found to induce memory impairments in animal models. However, it is still not understood how soluble ABeta alters the structure and function of synapses, especially in early stages of the disease. Dr. Calabrese hypothesizes that exposure of neurons to low levels of soluble ABeta results in definable changes in the numbers, shape, and stability of synapses. Pharmacological and gene transfer manipulations of synaptic ABeta targets will be used in combination with high resolution live cell imaging to test this hypothesis. These studies may provide novel insights to treat the earliest stages of AD, during which intervention is likely to be most effective. The hope is that by understanding soluble. ABeta-induced synaptic destabilization we can improve upon therapies that prevent synapse loss or restore synapse function.