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Biomarkers for Alzheimer’s disease—preparing for a new era of disease-modifying therapies

Molecular Psychiatry volume 26, pages 296–308 (2021)Cite this article

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Abstract

Clinical trial results presented in 2019 suggest that antibody-based removal of cerebral amyloid β (Aβ) plaques may possibly clear tau tangles and modestly slow cognitive decline in symptomatic Alzheimer’s disease (AD). Although regulatory approval of this approach is still pending, preparing the healthcare system for the advent of disease-modifying therapies against AD is imperative. In particular, it will be necessary to identify the most suitable biomarkers to facilitate appropriate treatment of AD. Here, we give an update on recent developments in fluid and imaging biomarkers for AD-related pathologies and discuss potential approaches that could be adopted to screen for and clarify the underlying pathology in people seeking medical advice because of cognitive symptoms. We succinctly review recent data regarding biomarkers for Aβ and tau pathology, neurodegeneration, synaptic dysfunction, and inflammation, highlight the need for further research into common copathologies, and suggest how different biomarkers could be used (most likely in combination) to facilitate the development and clinical implementation of novel drug candidates against AD.

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Fig. 1: Biomarkers for Alzheimer’s disease.
Fig. 2: Representative neuroimaging scans for assessing primary and secondary Alzheimer-related pathologies.
Fig. 3: A model of the temporal pattern of biomarker abnormalities for AD-related pathophysiological processes.

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Acknowledgements

HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931) and the UK Dementia Research Institute at UCL. BBB is supported by grants from the National Institute on Aging (P30AG062715, R01AG037639, RF1AG059312, R01AG062285, RF1AG057784, UF1AG051216).

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Authors and Affiliations

  1. Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden

    Henrik Zetterberg

  2. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden

    Henrik Zetterberg

  3. Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK

    Henrik Zetterberg

  4. UK Dementia Research Institute at UCL, London, UK

    Henrik Zetterberg

  5. Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA

    Barbara B. Bendlin

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  1. Henrik Zetterberg
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Correspondence to Henrik Zetterberg or Barbara B. Bendlin.

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Conflict of interest

HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. BBB has received precursors and imaging agents from Avid Radiopharmaceuticals.

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Zetterberg, H., Bendlin, B.B. Biomarkers for Alzheimer’s disease—preparing for a new era of disease-modifying therapies. Mol Psychiatry 26, 296–308 (2021). https://doi.org/10.1038/s41380-020-0721-9

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  • DOI: https://doi.org/10.1038/s41380-020-0721-9

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