Preclinical Longitudinal In Vivo Biomarker Platform for Alzheimer’s Disease Drug Discovery

The incorporation of target engagement, efficacy, and imaging abnormalities biomarkers on preclinical (animal) drug development brings the promise of accelerating drug development. In this chapter, we will highlight innovative methodological considerations that will bring greater predictive power relative to the traditional approaches in the preclinical stage of drug discovery. First, we discuss various animal models used in Alzheimer’s disease research and important aspects to consider when choosing the appropriate model to test a novel therapeutic intervention. Second, compared to the traditional histological methods, utilizing in vivo biomarkers in preclinical assessment allows quantifying disease pathophysiology with complex longitudinal designs. We discuss the feasibility and implications of longitudinal study designs and how the same in vivo biomarkers used in human clinical trials can be implemented to evaluate the preclinical development stages. Lastly, we discuss why the incorporation of methods from human clinical trials can advance the preclinical phases of drug discovery.