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Emerging diagnostics and therapeutics for Alzheimer disease

Nature Medicine volume 29, pages 2187–2199 (2023)Cite this article

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Abstract

Alzheimer disease (AD) is the most common contributor to dementia in the world, but strategies that slow or prevent its clinical progression have largely remained elusive, until recently. This Review highlights the latest advances in biomarker technologies and therapeutic development to improve AD diagnosis and treatment. We review recent results that enable pathological staging of AD with neuroimaging and fluid-based biomarkers, with a particular emphasis on the role of amyloid, tau and neuroinflammation in disease pathogenesis. We discuss the lessons learned from randomized controlled trials, including some supporting the proposal that certain anti-amyloid antibodies slow cognitive decline during the mildly symptomatic phase of AD. In addition, we highlight evidence for newly identified therapeutic targets that may be able to modify AD pathogenesis and progression. Collectively, these recent discoveries—and the research directions that they open—have the potential to move AD clinical care toward disease-modifying treatment strategies with maximal benefits for patients.

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Fig. 1: Select mechanisms contributing to neuronal dysfunction and degeneration during Alzheimer disease pathogenesis.
Fig. 2: Staging Alzheimer disease pathophysiology with fluid-based biomarkers.
Fig. 3: Pathophysiology beyond amyloid and tau.

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Acknowledgements

We thank E. Franke for assistance with the generation of figures. We acknowledge support from US National Institute of Health grants RF1NS090934, RF1AG047644 and U19AG069701, the JPB Foundation, the Cure Alzheimer’s Fund and the Rainwater Charitable Foundation (all to D.M.H.).

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  1. Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA

    Wade K. Self & David M. Holtzman

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Correspondence to David M. Holtzman.

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W.K.S. declares no competing interests. D.M.H. cofounded and is on the scientific advisory board of C2N Diagnostics. D.M.H. is on the scientific advisory board of Denali, Cajal Neuroscience and Genentech and consults for Asteroid Therapeutics. D.M.H. is an inventor on a patent on APOE antibodies that was licensed by Washington University to NextCure.

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Self, W.K., Holtzman, D.M. Emerging diagnostics and therapeutics for Alzheimer disease. Nat Med 29, 2187–2199 (2023). https://doi.org/10.1038/s41591-023-02505-2

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