Insights into CYP450 polymorphisms and their impact on drug metabolism in Alzheimer’s disease therapy

Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disorder that poses significant therapeutic challenges. Currently available treatments offer symptomatic relief but often yield suboptimal outcomes due to inter-individual variability in drug metabolism. Cytochrome P450 (CYP450) enzymes, particularly those exhibiting genetic polymorphisms, play a central role in the hepatic metabolism of many AD medications. This review focuses on the influence of CYP450 polymorphisms—specifically in CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4—on the pharmacokinetics, efficacy, and safety of approved anti-AD drugs. We discuss how variability in CYP450 expression and activity affects drug response, and examine the implications for adverse drug reactions, therapeutic failure, and dosage optimization. In addition, we evaluate current evidence for CYP450-mediated interactions with traditional Chinese medicines, which are increasingly used in complementary AD therapy. The potential for CYP450 genotyping and phenotyping to guide personalized treatment strategies is critically assessed. We argue that integrating pharmacogenomics into clinical practice may enhance therapeutic precision, reduce adverse outcomes, and improve quality of life in patients with AD. This review provides updated insight into the clinical significance of CYP450 polymorphisms in AD therapy and outlines future directions for personalized medicine approaches.