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In vitro evidence for a nonselective 4R tau PET tracer

Molecular Psychiatry (2023)Cite this article

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Aggregation of misfolded brain proteins is a common feature of several neurodegenerative diseases with the types of proteins, morphology, and spatial distribution often forming the defining pathological features for a given disease. Over the past two decades, considerable progress has been made towards developing positron emission tomography (PET) neuroimaging radioligands (i.e., radiotracers) targeting beta-amyloid (Aβ) plaques and neurofibrillary tau tangles, the pathological hallmarks of Alzheimer’s disease. PET imaging of Aβ and tau aggregates provides in vivo quantification of the density of underlying protein aggregates throughout the entire three-dimensional volume of the brain. To date, amyloid and tau PET imaging have been widely adopted to study the effects of Aβ and tau proteins on neurodegeneration and cognitive decline in Alzheimer’s disease, including use in clinical trials as inclusion/exclusion criteria, confirmation of target engagement, and as secondary trial endpoints. The interpretation of in vivo Aβ and tau PET imaging is highly informed by in vitro studies that characterize several aspects of PET tracers including binding affinity and selectivity of the radioligands to their designed molecular targets (see Mathis et al., for review [1]).

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Authors and Affiliations

  1. Division of Geriatrics, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA

    Tobey J. Betthauser

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

    Tobey J. Betthauser

  3. Department of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA

    Tobey J. Betthauser

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All contributions to this article including drafting and revising the manuscript were made by TJB.

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Correspondence to Tobey J. Betthauser.

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Competing interests

TJB has received funding from the Alzheimer’s Association and the National Institute on Aging under the grants listed below but has no other relevant disclosures. NIH/NIA R01AG021155, RF1AG027161, R01AG062285, P30AG062715, R01AG070883 and the Alzheimer’s Association AARF-19-614533.

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Betthauser, T.J. In vitro evidence for a nonselective 4R tau PET tracer. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-01950-2

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