Cleary, James P., Ph.D.

ALZHEIMER'S DISEASE/BRAIN SCIENCES

Our research is focused on behavioral and CNS effects of Alzheimer's disease (AD). One major area of interest is the neurotoxic and behavioral effects of the beta amyloid peptide. Beta amyloid peptide (A_) is the major component of the plaques found in the brains of patients suffering from Alzheimer's disease, and is implicated in the cascade of neurological events leading to neural and behavioral pathogenesis. We have recently shown that a narrow range of conformations of the A_ peptide at physiologically relevant concentrations can produce memory loss in animals. This was accomplished by first developing a sensitive rat bioassay for AD-like symptoms, including deficits in learning and memory, and through collaboration with scientists capable of producing the specific conformations of A_. In another study we have shown beneficial effects of common anti-inflammatory drugs in this same model of AD. We also use transgenic mouse models of Alzheimer's disease to assess potential therapeutic interventions. These animals develop amyloid plaques and show age-dependent memory deficits similar to those seen in AD. We characterized the behavior of these mice under several behavioral protocols, including those for motivation, attention, perception and memory. We have recently shown that non-steroidal anti-inflammatory drugs can have beneficial effects on learned behavior and in these mice. Finally, we have obtained a new transgenic mouse model of AD, from Dr. Karen Ashe that expresses a more complete phenotype, including age-related memory loss, A_ plaque development, and hyperphosphorylated tau. We are currently working with this model to assess the contributions of each protein to cognitive deficits.