The strategic biomarker roadmap for the validation of Alzheimer’s diagnostic biomarkers: methodological update

Research output: Contribution to journalArticle


Background: The 2017 Alzheimer’s disease (AD) Strategic Biomarker Roadmap (SBR) structured the validation of AD diagnostic biomarkers into 5 phases, systematically assessing analytical validity (Phases 1–2), clinical validity (Phases 3–4), and clinical utility (Phase 5) through primary and secondary Aims. This framework allows to map knowledge gaps and research priorities, accelerating the route towards clinical implementation. Within an initiative aimed to assess the development of biomarkers of tau pathology, we revised this methodology consistently with progress in AD research. Methods: We critically appraised the adequacy of the 2017 Biomarker Roadmap within current diagnostic frameworks, discussed updates at a workshop convening the Alzheimer’s Association and 8 leading AD biomarker research groups, and detailed the methods to allow consistent assessment of aims achievement for tau and other AD diagnostic biomarkers. Results: The 2020 update applies to all AD diagnostic biomarkers. In Phases 2–3, we admitted a greater variety of study designs (e.g., cross-sectional in addition to longitudinal) and reference standards (e.g., biomarker confirmation in addition to clinical progression) based on construct (in addition to criterion) validity. We structured a systematic data extraction to enable transparent and formal evidence assessment procedures. Finally, we have clarified issues that need to be addressed to generate data eligible to evidence-to-decision procedures. Discussion: This revision allows for more versatile and precise assessment of existing evidence, keeps up with theoretical developments, and helps clinical researchers in producing evidence suitable for evidence-to-decision procedures. Compliance with this methodology is essential to implement AD biomarkers efficiently in clinical research and diagnostics.


  • Marina Boccardi
  • Alessandra Dodich
  • Emiliano Albanese
  • Angèle Gayet-Ageron
  • Cristina Festari
  • Nicholas J. Ashton
  • Gérard N. Bischof
  • Konstantinos Chiotis
  • Emma E. Wolters
  • Martin A. Walter
  • Gil D. Rabinovici
  • Maria Carrillo
  • Alexander Drzezga
  • Agneta Nordberg
  • Victor L. Villemagne
  • Bengt Winblad
  • Giovanni B. Frisoni
  • Valentina Garibotto
External organisations
  • University of Geneva
  • University of Trento
  • University of Lugano
  • Geneva University Hospital
  • Centro San Giovanni di Dio Fatebenefratelli
  • South London and Maudsley NHS Foundation Trust
  • King's College London
  • University Hospital of Cologne
  • Karolinska Institutet
  • Karolinska University Hospital
  • University of California, San Francisco
  • University of Cologne
  • Jülich Research Centre
  • Skåne University Hospital
  • Vrije Universiteit Amsterdam
  • Amsterdam UMC - Vrije Universiteit Amsterdam
  • Austin Health
  • University of Pittsburgh
  • University of Gothenburg
  • Alzheimer's Association: Alzheimer's Disease and Dementia
  • German Center for Neurodegenerative Diseases (DZNE), Bonn
  • German Center for Neurodegenerative Diseases (DZNE), Greifswald
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology


  • Alzheimer’s disease, Biomarker, Dementia, MCI, Mild cognitive impairment, Validation methodology
Original languageEnglish
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Publication statusE-pub ahead of print - 2021
Publication categoryResearch