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Blood biomarkers for Alzheimer’s disease in clinical practice and trials

Nature Aging volume 3, pages 506–519 (2023)Cite this article

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Abstract

Blood-based biomarkers hold great promise to revolutionize the diagnostic and prognostic work-up of Alzheimer’s disease (AD) in clinical practice. This is very timely, considering the recent development of anti-amyloid-β (Aβ) immunotherapies. Several assays for measuring phosphorylated tau (p-tau) in plasma exhibit high diagnostic accuracy in distinguishing AD from all other neurodegenerative diseases in patients with cognitive impairment. Prognostic models based on plasma p-tau levels can also predict future development of AD dementia in patients with mild cognitive complaints. The use of such high-performing plasma p-tau assays in the clinical practice of specialist memory clinics would reduce the need for more costly investigations involving cerebrospinal fluid samples or positron emission tomography. Indeed, blood-based biomarkers already facilitate identification of individuals with pre-symptomatic AD in the context of clinical trials. Longitudinal measurements of such biomarkers will also improve the detection of relevant disease-modifying effects of new drugs or lifestyle interventions.

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Fig. 1: Suggested blood-based biomarker-based workflow for Alzheimer’s disease diagnostics.
Fig. 2: An overview of key blood-based biomarkers used in the diagnostic or prognostic work-up of Alzheimer’s disease.
Fig. 3: Suggested workflow for inclusion of study participants into preclinical Alzheimer’s disease trials.

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Acknowledgements

O.H. was supported by the Swedish Research Council (2022-00775), ERA PerMed (ERAPERMED2021-184), the Knut and Alice Wallenberg Foundation (2017-0383), the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s disease) at Lund University, the Swedish Alzheimer Foundation (AF-980907), the Swedish Brain Foundation (FO2021-0293), the Parkinson Foundation of Sweden (1412/22), the Cure Alzheimer’s Fund, the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, the Skåne University Hospital Foundation (2020-O000028), Regionalt Forskningsstöd (2022-1259) and the Swedish federal government under the ALF agreement (2022-Projekt0080). K.B. is supported by the Swedish Research Council (2017-00915 and 2022-00732; 1 January 2023 to 31 December 2026), the Alzheimer Drug Discovery Foundation, USA (RDAPB-201809-2016615), the Swedish Alzheimer Foundation (AF-930351, AF-939721 and AF-968270), Hjärnfonden, Sweden (FO2017-0243 and ALZ2022-0006), the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (ALFGBG-715986 and ALFGBG-965240), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), the National Institutes of Health, USA (grant 1R01AG068398-01), the Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495) and the Alzheimer’s Association 2022–2025 grant (SG-23-1038904 QC). H.Z. is a Wallenberg Scholar supported by grants from the Swedish Research Council (2018-02532), the European Union’s Horizon Europe research and innovation program under grant agreement 101053962, Swedish State Support for Clinical Research (ALFGBG-71320), the Alzheimer Drug Discovery Foundation, USA (201809-2016862), the AD Strategic Fund and the Alzheimer’s Association (ADSF-21-831376-C, ADSF-21-831381-C and ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (FO2022-0270), the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement 860197 (MIRIADE), the European Union Joint Programme, Neurodegenerative Disease Research (JPND2021-00694) and the UK Dementia Research Institute at UCL (UKDRI-1003).

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Authors and Affiliations

  1. Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden

    Oskar Hansson

  2. Memory Clinic, Skåne University Hospital, Lund, Sweden

    Oskar Hansson

  3. Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden

    Kaj Blennow & Henrik Zetterberg

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

    Kaj Blennow & Henrik Zetterberg

  5. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK

    Henrik Zetterberg

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

    Henrik Zetterberg

  7. Hong Kong Center for 27 Neurodegenerative Diseases, Hong Kong, China

    Henrik Zetterberg

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

    Henrik Zetterberg

  9. Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA

    Jeffrey Dage

  10. Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA

    Jeffrey Dage

  11. Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA

    Jeffrey Dage

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Contributions

O.H. was mainly responsible for drafting and revising the manuscript, and he handled the correspondence. K.B., H.Z. and J.D. contributed substantially to the both drafting and revision of the manuscript.

Corresponding author

Correspondence to Oskar Hansson.

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Competing interests

O.H. has acquired research support (for the institution) from ADx, Avid Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer and Roche. In the past 2 years, he has received consultancy and/or speaker fees from AC Immune, Amylyx, ALZpath, BioArctic, Biogen, Cerveau, Eisai, Fujirebio, Genentech, Novartis, Roche and Siemens. K.B. has served as a consultant on advisory boards or on data-monitoring committees for Abcam, Axon, BioArctic, Biogen, JOMDD–Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Ono Pharma, Pharmatrophix, Prothena, Roche Diagnostics and Siemens Healthineers and is a cofounder of Brain Biomarker Solutions in Gothenburg (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. H.Z. has served on scientific advisory boards and/or as a consultant for AbbVie, Acumen, Alector, Alzinova, ALZpath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, NervGen, Novo Nordisk, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics and Wave; has given lectures in symposia sponsored by Cellectricon, Fujirebio, AlzeCure, Biogen and Roche; and is a cofounder of Brain Biomarker Solutions in Gothenburg (BBS), which is a part of the GU Ventures Incubator Program (outside the work presented in this paper). J.D. is an inventor on patents or patent applications of Eli Lilly relating to the assays, methods, reagents and/or compositions of matter related to measurement of p-tau217. J.D. has served as a consultant for AbbVie, Genotix Biotechnologies, Gates Ventures, Karuna Therapeutics, ALZpath and Cognito Therapeutics and received research support from ADx NeuroSciences, Fujirebio, ALZpath, Roche Diagnostics and Eli Lilly in the past 2 years. J.D. has received speaker fees from Eli Lilly.

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Hansson, O., Blennow, K., Zetterberg, H. et al. Blood biomarkers for Alzheimer’s disease in clinical practice and trials. Nat Aging 3, 506–519 (2023). https://doi.org/10.1038/s43587-023-00403-3

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