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Synapses are points of contact between nerve cells and facilitate transmission of information. Loss of synapses in AD contributes to the loss of memory function. Calpains (I, II and III) are enzymes that are activated by high levels of calcium and can destroy synaptic proteins that are important for normal brain cell functioning. Calpains may also play a role in the regulation of APP processing. APP is the parent protein from which b-amyloid is derived. Using cell and animals models, Dr. Arancio aims to determine if it is possible to prevent the loss of synapses and increased b-amyloid associated with calpain activation by administration of compounds that inhibit calpains (I, II and III).