Grant: Operating Grant

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common form of dementia in the elderly. The prime candidate for the cause of Alzheimer's disease is the peptide beta-amyloid (A-beta), which is formed by biochemical processing of the amyloid precursor protein (APP), and is part of the plaques found in the brain of AD patients. However, memory deficits in AD patients do not correlate well with A-beta plaque burden, but, rather, with the loss of synaptic markers. Synaptic plasticity is the best cellular approach available for how learning and memory occurs in the brain, and it was, therefore, of great interest that the rules for synaptic plasticity are changed in animal models of Alzheimer's disease. How these changes take place, however, is largely unknown. Therefore, we propose a set of experiments to examine how the different parts of APP, such as A-beta, affect synaptic plasticity and, thereby, affect learning and memory. We hope to further elucidate the mechanisms underlying Alzheimer's disease as well as provide potential targets for future AD treatments.