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The biomarker roadmap for the validation for Alzheimer’s biomarkers: Methodological update for biomarkers of tauopathy
Author(s) -
Boccardi Marina,
Dodich Alessandra,
Albanese Emiliano,
GayetAgeron Angèle,
Walter Martin,
Rabinovici Gil D.,
Carrillo Maria C.,
Drzezga Alexander,
Hansson Oskar,
Nordberg Agneta K,
Ossenkoppele Rik,
Villemagne Victor L.L.,
Teipel Stefan J.,
Winblad Bengt,
Garibotto Valentina,
Frisoni Giovanni B.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.039063
Subject(s) - biomarker , tauopathy , biomarker discovery , medicine , disease , psychology , pathology , proteomics , biology , neurodegeneration , biochemistry , gene
Background The 2017 Alzheimer’s disease (AD) Biomarker Roadmap structures the validation of AD diagnostic biomarkers into a systematic sequence of 5 Phases, each encompassing primary and secondary aims assessing analytical validity (Phases 1‐2), clinical validity (Phases 3‐4) and clinical utility (Phase 5). This framework allows us to assess current evidence and identify requirements, gaps, and research priorities towards Phase‐5 validity. While using this methodology to assess the validation status of biomarkers of tau pathology we revised this methodology consistently with progresses in AD research. Method First, we critically appraised the adequacy of the 2017 Biomarker Roadmap to assess tau biomarkers and relative to the current biomedical perspective of AD (e.g., A/T/N framework). Second, we proposed and discussed the adaptations at a workshop (Geneva, November 11‐12, 2019) convening the Alzheimer’s Association and 8 leading AD biomarker research groups, tasked with assessing the validity of CSF‐, plasma‐ and imaging‐tau biomarkers for AD according to the updated Biomarker Roadmap framework. Result The 2019 updates apply to tau as well as other biomarkers and include: Phase 3: a greater variety of study designs (e.g., cross‐sectional in addition to longitudinal) and reference standards (e.g., AD biomarker confirmation in addition to clinical progression) deemed appropriate to appraise the evidence on tau biomarkers; Phases 1‐5:evidence appraisal examining quality of evidence in addition to target results. Most urgent research priorities for both tau and other biomarkers are to: Define specific clinically‐ and patient‐relevant outcomes with all pertinent stakeholders (patients, caregivers, clinicians, regulators), to prepare proper studies on clinical utility and implementation; Produce/adapt specific reporting guidelines facilitating methodological compliance, reporting and assessment of the produced evidence. Conclusion We have revised the Biomarker Roadmap accommodating biomarkers of tau pathology. This revision improves the methodology also for the other AD biomarkers. To further boost their validation up to Phase‐5 studies, the available evidence should be assessed by methodologists not directly involved in the assessed studies, possibly through dynamic data sharing on accessible platforms. Compliance with this methodology is essential to implement tau biomarkers efficiently in clinical research and diagnostics.