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Chapter 13 - Use of rodent models in drug discovery for Alzheimer’s disease
Book chapter

Chapter 13 - Use of rodent models in drug discovery for Alzheimer’s disease

James E. Barrett, Joanne R. Mathiasen and Paul McGonigle
Drug Discovery Approaches for the Treatment of Neurodegenerative Disorders, pp 359-374
2026
DOI: https://doi.org/10.1016/B978-0-443-30008-0.00018-1

Abstract

Alzheimer’s disease Contextual fear conditioning Morris water maze Presenilin Rodent models Swedish mutation
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 co-morbidities such as depression, 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. The discovery of discrete mutations linked to familial AD and genetic risk factors for the more common sporadic or late onset AD has enabled the creation of a multitude of transgenic mouse models. 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. Transgenic mouse models have been instrumental in the development of recently approved disease modifying therapeutic antibodies.

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