Christopher B. Eckman, Ph.D.
Michael Hutton, Ph.D.

Alzheimer's Disease Drug Discovery and Evaluation

Pathological hallmarks of Alzheimer's disease (AD) include the presence of significant numbers of extracellular protein deposits referred to as "senile plaques" and intraneuronal inclusions known as "neurofibrillary tangles". While the self-aggregating Abeta peptide is the predominant proteinaceous component of the senile plaques, neurofibrillary tangles are comprised predominantly of an abnormal accumulation of the neurofilament protein tau. The abnormal accumulation of these proteins is believed to play pivotal roles in the etiology and pathogenesis of AD. Therefore strategies that reduce these protein accumulations might be therapeutic. We propose

1. To further evaluate the effects of identified as AP reducing agents on AP accumulation and other aspects of I3APP processing in cell based models.
2. To establish a tau screening assay similar to the one we have previously developed for AI3 and to screen our compound libraries for agents that influence tau levels
3. To examine the effect of identified compounds on tau and AP concentration and abnormal accumulation in appropriate mouse models.