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Role of Pharmacogenomics in Individualizing Treatment for Alzheimer’s Disease

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Abstract

The development of Alzheimer’s disease therapeutics has been challenging, with 99% of clinical trials failing to find a significant difference between drug and placebo. While the quest continues for more effective treatments, there is emerging evidence that pharmacogenetic considerations are important factors in regard to metabolism, efficacy, and toxicity of drugs. Currently, there are five US Food and Drug Administration-approved drugs for the treatment of Alzheimer’s disease; three acetylcholinesterase inhibitors, memantine, and aducanumab. Introducing a limited genetic panel consisting of APOE4, CYP2D6*10, and BChE*K would optimize acetylcholinesterase inhibitor therapy, facilitate immunotherapy risk assessment, and inform an amyloid-related imaging abnormality surveillance schedule. In view of the genetic heterogeneity of Alzheimer’s disease identified in genome-wide association studies, pharmacogenetics is expected to play an increasing role in mechanism-specific treatment strategies and personalized medicine.

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Acknowledgements

We thank the patients and their families for participating in these trials.

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  1. State University of New York at Buffalo, 875 Ellicott St., Buffalo, NY, 14203, USA

    Natalie Argueta, Emily Notari & Kinga Szigeti

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  1. Natalie Argueta
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Correspondence to Kinga Szigeti.

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N.A. performed the literature search, wrote the first draft of the manuscript, and designed the supplementary tables. E.N. critically revised the manuscript. K.S. formulated the idea for the publication and critically revised the manuscript and the supplementary tables. All authors have read and approve the final submitted version of the paper and agree to be accountable for this work.

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Argueta, N., Notari, E. & Szigeti, K. Role of Pharmacogenomics in Individualizing Treatment for Alzheimer’s Disease. CNS Drugs 36, 365–376 (2022). https://doi.org/10.1007/s40263-022-00915-3

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