Clinical validity of increased cortical binding of tau ligands of the THK family and PBB3 on PET as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework
Year: 2021
Type: article
Abstract: PURPOSE: The research community has focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer's disease (AD). In 2017, the Geneva AD Biomarker Roadmap initiative adapted the framework for the systematic validation of oncological biomarkers to AD, with the aim to accelerate their development and implementation in clinical practice. The aim of this work was to assess the validation status of tau PET ligands of the THK family and PBB3 as imaging biomarkers for AD, based on the Biomarker Roadmap methodology. METHODS: A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva. The level of clinical validity of tau PET ligands of the THK family and PBB3 was assessed based on the 5-phase development framework before the meeting and discussed during the workshop. RESULTS: PET radioligands of the THK family discriminate well between healthy controls and patients with AD dementia (phase 2; partly achieved) and recent evidence suggests an accurate diagnostic accuracy at the mild cognitive impairment (MCI) stage of the disease (phase 3; partly achieved). The phases 2 and 3 were considered not achieved for PBB3 since no evidence exists about the ligand's diagnostic accuracy. Preliminary evidence exists about the secondary aims of each phase for all ligands. CONCLUSION: Much work remains for completing the aims of phases 2 and 3 and replicating the available evidence. However, it is unlikely that the validation process for these tracers will be completed, given the presence of off-target binding and the development of second-generation tracers with improved binding and pharmacokinetic properties.
Institutions: Karolinska University Hospital, Karolinska Institutet, University of Geneva, University of Trento, German Center for Neurodegenerative Diseases, Centro San Giovanni di Dio Fatebenefratelli, Forschungszentrum Jülich, University of Cologne, Lund University, Skåne University Hospital, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam UMC Location Vrije Universiteit Amsterdam, 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, Eli Lilly and Company, Pfizer, Biogen, Velux Stiftung, Loo och Hans Ostermans Stiftelse för Medicinsk Forskning, Demensförbundet, Stiftelsen för Gamla Tjänarinnor, Cerveau Technologies, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Stiftelsen för Strategisk Forskning, Fondation pour la Recherche Médicale, Svenska Sällskapet för Medicinsk Forskning, Hjärnfonden, Karolinska Institutet, Vetenskapsrådet, Åhlén-stiftelsen, Siemens Healthineers, Avid Radiopharmaceuticals, Center for Innovative Medicine
Awards: Proteinopathies in neurodegenerative disorders-new imaging biomarkers for early disease detection and new drug targets, G1855244678, G2336828072, G3869307713, 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, G5729005898, The Biological Basis of Cognitive Impairment due to Suspected Non-Alzheimer’s Pathology (SNAP) : Studying the interplay between amyloidosis and tau-related neurodegeneration, G8150425658, G8229001562, G880118091, Nya biomarkörer vid tidig diagnos och behandling av AD
OpenAlex ID: W3135986468