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Alzheimer’s disease biomarkers and their current use in clinical research and practice

Molecular Psychiatry (2024)Cite this article

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Abstract

While blood-based tests are readily available for various conditions, including cardiovascular diseases, type 2 diabetes, and common cancers, Alzheimer’s disease (AD) and other neurodegenerative diseases lack an early blood-based screening test that can be used in primary care. Major efforts have been made towards the investigation of approaches that may lead to minimally invasive, cost-effective, and reliable tests capable of measuring brain pathological status. Here, we review past and current technologies developed to investigate biomarkers of AD, including novel blood-based approaches and the more established cerebrospinal fluid and neuroimaging biomarkers of disease. The utility of blood as a source of AD-related biomarkers in both clinical practice and interventional trials is discussed, supported by a comprehensive list of clinical trials for AD drugs and interventions that list biomarkers as primary or secondary endpoints. We highlight that identifying individuals in early preclinical AD using blood-based biomarkers will improve clinical trials and the optimization of therapeutic treatments as they become available. Lastly, we discuss challenges that remain in the field and address new approaches being developed, such as the examination of cargo packaged within extracellular vesicles of neuronal origin isolated from peripheral blood.

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Fig. 1: The number of AD-clinical trials listing biomarkers as primary or secondary endpoints from 2000 to 2024.
Fig. 2: The number of primary or secondary biomarker endpoints in interventional trials across phase 3, phase 4, or FDA-approved AD therapeutics.

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Authors and Affiliations

  1. Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada

    Tai R. Hunter & Fernanda G. De Felice

  2. D’Or Institute for Research and Education, Rio de Janeiro, RJ, Brazil

    Luis E. Santos, Fernanda Tovar-Moll & Fernanda G. De Felice

  3. Centre for Neuroscience Studies and Department of Psychiatry, Queen’s University, Kingston, ON, Canada

    Fernanda G. De Felice

  4. Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Fernanda G. De Felice

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FGDF and TRH conceptualized the article. TRH wrote the original draft. TRH and LES created the figures and tables. TRH, LES, FTM, and FGDF reviewed and edited the manuscript. All authors approve the submission of the manuscript.

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Hunter, T.R., Santos, L.E., Tovar-Moll, F. et al. Alzheimer’s disease biomarkers and their current use in clinical research and practice. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02709-z

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