Evaluation of dopaminergic mechanisms in the DM tau mouse

点击翻译按钮获取中文摘要

ABSTRACT Psychotic Alzheimer’s disease (AD+P) is a distinct AD variant with a more rapid cognitive deterioration and a hastened mortality for which safe and effective treatment is lacking. CSF biomarker and neuropathological studies suggest that AD+P results from an acceleration of tau phosphorylation. The development of novel compounds to treat AD+P would be facilitated by the development of a preclinical behavioral model, made possible by neuropathological correlation studies that uniquely identify tau phosphorylation in psychosis risk. The NIMH Research Domain Criteria (RDoC) initiative provides a framework for the transdiagnostic conceptualization of psychosis risk driven by dopamine, and has been incorporated in the design of a novel candidate behavioral model of AD+P that is characterized by increased dopaminergic tone and hyperphophorylated tau- the DM mouse. In the proposed application the DM and other tau models will be utilized in order to investigate dopamine in a pharmacological induction paradigm of AD+P, and in order to study the relationship between tau phosphorylation and psychosis-relevant behaviors. The completion of the proposed set of experiments may point the way to further research in the development of a preclinical avenue for drug development in the treatment of AD+P.