The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers
Year: 2021
Type: article
Abstract: PURPOSE: The development of blood biomarkers that reflect Alzheimer's disease (AD) pathophysiology (phosphorylated tau and amyloid-β) has offered potential as scalable tests for dementia differential diagnosis and early detection. In 2019, the Geneva AD Biomarker Roadmap Initiative included blood biomarkers in the systematic validation of AD biomarkers. METHODS: A panel of experts convened in November 2019 at a two-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of blood biomarkers was assessed based on the Biomarker Roadmap methodology and discussed fully during the workshop which also evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. RESULTS: Plasma p-tau has shown analytical validity (phase 2 primary aim 1) and first evidence of clinical validity (phase 3 primary aim 1), whereas the maturity level for Aβ remains to be partially achieved. Full and partial achievement has been assigned to p-tau and Aβ, respectively, in their associations to ante-mortem measures (phase 2 secondary aim 2). However, only preliminary evidence exists for the influence of covariates, assay comparison and cut-off criteria. CONCLUSIONS: Despite the relative infancy of blood biomarkers, in comparison to CSF biomarkers, much has already been achieved for phases 1 through 3 - with p-tau having greater success in detecting AD and predicting disease progression. However, sufficient data about the effect of covariates on the biomarker measurement is lacking. No phase 4 (real-world performance) or phase 5 (assessment of impact/cost) aim has been tested, thus not achieved.
Institutions: King's College London, Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Lund University, Skåne University Hospital, University of Geneva, University of Trento, German Center for Neurodegenerative Diseases, Centre National de la Recherche Scientifique, University of Cologne, University Hospital Cologne, Karolinska University Hospital, Karolinska Institutet, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam UMC Location Vrije Universiteit Amsterdam, Sahlgrenska University Hospital, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, University College London, University Hospital of Geneva
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,480
Funders: National Science Foundation, Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Parkinson Research Foundation, Australian Government, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Lunds Universitet, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Göteborgs Universitet, Marcus och Amalia Wallenbergs minnesfond, Stiftelsen Bundy Academy, Parkinsonfonden
Awards: Individual cognitive risk profiling in aging according to Amyloid, Tau and Neurodegeneration imaging biomarkers, Strategic roadmap for the translation of tau biomarkers in the clinic: an international task force, The Biological Basis of Cognitive Impairment due to Suspected Non-Alzheimer’s Pathology (SNAP) : Studying the interplay between amyloidosis and tau-related neurodegeneration, G880118091
OpenAlex ID: W3135004658