Non human primate models for Alzheimer’s disease-related research and drug discovery

ABSTRACT Introduction: Pathophysiological mechanisms underlying Alzheimer’s disease (AD) remain insufficiently documented for the identification of accurate diagnostic markers and purposeful target discovery and development. Nonhuman primates (NHPs) have important translational value given their close phylogenetic relationship to humans and similar developmental paths in (neuro)anatomy, physiology, genetics, and neural functions, as well as cognition, emotion, and social behavior. Areas covered: This review deals with the past and future role of NHP-based research in AD pathophysiology, diagnosis and drug discovery, and touches upon ethical and legal aspects. Expert opinion: Aging NHPs are not complete phenocopies of human AD. Conceivably, no other species or experimental model will ever develop the full spectrum of AD-typical alterations. Nevertheless, partial – and even negative – models can increase knowledge of disease mechanisms. Modeling complex brain disorders should not be based on a single model or species. Understanding brain diseases relies on knowledge of healthy brain functioning, and given their close phylogenetic relationship to humans, NHPs serve excellent tools in this respect. NHP-based studies remain essential in the development and validation of radiopharmaceuticals for early diagnostic imaging biomarkers, as well as in the efficacy and safety evaluation of new therapeutic approaches, with active immunization or vaccination approaches as front runners.