Abstract

Alzheimer’s disease (AD) is a devastating and untreatable disorder characterized by dementia and the accumulation of aggregated tau protein in the brain. Tau is normally found in healthy neurons, in which the majority of it binds to microtubules and facilitates neuronal functions. A small fraction of tau is usually “free”from microtubules to interact with other proteins, including itself. Indeed, this “free” tau population is thought to be much more prone to aggregation and harder for a neuron to remove. Our laboratory has focused on understanding the pathways that keep tau at a balanced level in the brain, and we hypothesize that age-associated failure of these mechanisms is a major culprit in AD. Specifically, I am interested in mechanisms that can preferentially remove “free” tau. My current research focuses on using chemical and genetic methods to identify and characterize these mechanisms. My key hypothesis is that removing “free” tau by activating these mechanisms will provide potential treatments for AD. Moreover, I am also developing drug-like small molecules that can preferentially accelerate the removal of “free” tau.