Review Article | Published:

Imaging tau and amyloid-β proteinopathies in Alzheimer disease and other conditions

Nature Reviews Neurology volume 14, pages 225236 (2018) | Download Citation

This article has been updated

Abstract

Most neurodegenerative disorders are associated with aggregated protein deposits. In the case of Alzheimer disease (AD), extracellular amyloid-β (Aβ) aggregates and intracellular tau neurofibrillary tangles are the two neuropathological hallmarks of the disease. Aβ-PET imaging has already been approved for clinical use and is being used in clinical trials of anti-Aβ therapies both for patient recruitment and as an outcome measure. These studies have shown that Aβ accumulation is a protracted process that can extend for more than 2 decades before the onset of clinical AD. This Review describes how in vivo brain imaging of Aβ pathology has revolutionized the evaluation of patients with clinical AD by providing robust and reproducible statements of global or regional brain Aβ burden and enabling the monitoring of disease progression. The role of selective tau imaging is discussed, focusing on how longitudinal tau and Aβ imaging studies might reveal the various effects (sequential and/or parallel, independent and/or synergistic) of these proteins on progression, cognition and other disease-specific biomarkers of neurodegeneration. Finally, imaging studies are discussed in the context of elucidating the respective roles of Aβ and tau in AD and in advancing our understanding of the relationship and/or interplay between these two proteinopathies.

Key points

  • The clinical phenotypes of patients with proteinopathies do not always enable identification of the underlying cause of the disorder, especially in early disease

  • By contrast, biochemical and imaging biomarkers can identify, even at presymptomatic stages, the underlying proteinopathy likely to cause the disease

  • Imaging biomarkers of pathology and neuronal injury can also help to stage these diseases

  • Amyloid-β and tau imaging studies can aid in patient selection, assess target engagement and monitor intervention efficacy in disease-specific treatment trials

  • Incorporation of biochemical and imaging biomarkers into new diagnostic criteria for Alzheimer disease offers a rational and flexible diagnostic approach that does not require the presence of dementia

  • Integration of biochemical and imaging biomarker findings with cognitive assessment is also expected to improve the predictive paradigm for Alzheimer disease

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Change history

  • 07 June 2018

    In Figure 1 of this article as originally published, the chemical structure at bottom right was incorrectly labelled 18F-PM-PBB3. The text label has been corrected to 18F-PBB3 in the PDF and HTML versions of the article. As of this date, the structure of PM-PBB3 (also known as APN-1607) has not yet been published.

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Acknowledgements

The authors thank S. Laws, G. R. Mulligan, G. Savage, J. Robertson, S. Bozinovski, D. El-Sheikh and the Brain Research Institute for their assistance with the preparation of this Review. The authors' research work is supported in part by project grants 1044361, 1011689 and 1071430 from the National Health and Medical Research Council of Australia to C.C.R. and V.L.V.

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Affiliations

  1. Department of Molecular Imaging and Therapy, Centre for PET, Austin Health, Heidelberg, Victoria, Australia.

    • Victor L. Villemagne
    • , Vincent Doré
    •  & Christopher C. Rowe
  2. Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.

    • Victor L. Villemagne
    •  & Christopher C. Rowe
  3. The Florey Institute of Neuroscience and Mental Health and University of Melbourne, Parkville, Victoria, Australia.

    • Victor L. Villemagne
    • , Colin L. Masters
    •  & Christopher C. Rowe
  4. CSIRO, Health and Biosecurity Flagship, The Australian eHealth Research Centre, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.

    • Vincent Doré
  5. eHealth, CSIRO Health and Biosecurity, Melbourne, Parkville, Victoria, Australia.

    • Samantha C. Burnham

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Contributions

V.L.V. wrote the manuscript. V.L.V., V.D., S.C.B. and C.C.R. researched data for the article, and V.D., S.C.B., C.L.M. and C.C.R. contributed substantially to discussions of its content. All authors undertook review and/or editing of the manuscript before submission.

Competing interests

V.L.V. declares that he has received consultancy fees from AbbVie, Hoffmann-La Roche, Lundbeck, Novartis and Shanghai Green Valley Pharmaceutical as well as honoraria for speaking from AbbVie, AstraZeneca, Avid Radiopharmaceuticals, GE Healthcare, Hoffmann-La Roche and Piramal Imaging. C.L.M. declares that he owns stock in or is a company director of Prana Biotechnology. C.C.R. declares that he has received consultancy fees from AstraZeneca, Avid Radiopharmaceuticals, Biogen, GE Healthcare and Piramal Imaging as well as honoraria for speaking from AbbVie, AstraZeneca, Avid Radiopharmaceuticals, GE Healthcare, Hoffmann-La Roche and Piramal Imaging and grants or research support from AstraZeneca, Avid Radiopharmaceuticals, Biogen, GE Healthcare and Piramal Imaging. V.D. and S.C.B. declare no competing interests.

Corresponding author

Correspondence to Victor L. Villemagne.

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DOI

https://doi.org/10.1038/nrneurol.2018.9

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