ABSTRACT

Alzheimer’s disease (AD) is a multifaceted and progressive neurodegenerative disorder that currently lacks effective treatments. This has prompted significant research efforts to develop new anti-AD drugs. Before advancing to clinical trials, it is crucial to evaluate the safety and efficacy of these drugs using preclinical models. This book chapter discusses the in vivo and in vitro methods for evaluating anti-AD drugs in preclinical research. The in vivo approaches discussed in this chapter include transgenic animal models, nontransgenic animal models, and ex vivo models. Transgenic models, such as the APP/PS1 mouse model, express mutant genes that cause AD-like pathology and are widely used to study AD pathophysiology and evaluate potential therapies. Nontransgenic models, such as the scopolamine-induced amnesia model, mimic AD-like symptoms and are useful for testing drug efficacy. Ex vivo models, such as brain slice cultures and primary neuronal cultures, offer a simplified system for studying the effects of drug effects inside the cellular system. The in vitro methods described in this chapter include cell-based assays and biochemical assays. Cell-based assays, such as the Aβ aggregation assay and the tau hyperphosphorylation assay, measure drug effects on specific cellular pathways involved in AD pathology. Biochemical assays, such as the acetylcholinesterase inhibition assay and the antioxidant activity assay, evaluate the potential of drugs to modulate specific biochemical targets in AD. In summary, this book chapter provides a comprehensive overview of the preclinical approaches used to evaluate anti-AD drugs. Understanding the strengths and limitations of these approaches is critical for advancing potential therapies toward clinical trials and ultimately improving outcomes for individuals with AD.