Rodent Models for Alzheimer's Disease in Drug Discovery

Abstract

One of the cornerstones of translational research is the use of animal model systems, typically rodents, to inform drug discovery efforts about the potential therapeutic utility of a preclinical compound. A wide variety of pharmacological and genetic models have been developed to incorporate the neurochemical and pathological components of Alzheimer's disease (AD). The complex etiology and heterogeneous pathology of this disease, together with the associated comorbidities such as depression and psychotic-like behavior such as paranoia pose significant challenges for animal model development and for the use of these models to facilitate the development of new drugs. A single model of AD that faithfully reflects both the pathological aspects as well as the behavioral phenotypes is unlikely. However, knowledge of the different models available and a detailed understanding of their features, including specifics of the background strain of a transgenic mouse, the specific mutation, and the progression of both pathological and behavioral changes can aid in selection and characterization of new therapeutics.