Insights into the use of biomarkers in clinical trials in Alzheimer's disease
Tharick A. Pascoal,
Cristiano S. Aguzzoli,
Firoza Z. Lussier,
Lucía Crivelli,
Claudia K. Suemoto,
Juan Fortea,
Pedro Rosa-Neto,
Eduardo R. Zimmer,
Pamela C.L. Ferreira,
Bruna Bellaver
Affiliations
Tharick A. Pascoal
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA; Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA; Corresponding author. Department of Psychiatry and Neurology, University of Pittsburgh, 3501 Forbes Avenue – Oxford Building, 15213, Pittsburgh, PA, USA.
Cristiano S. Aguzzoli
Brain Institute of Rio Grande do Sul, PUCRS, Porto Alegre, Brazil
Firoza Z. Lussier
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA
Lucía Crivelli
Department of Cognitive Neurology, Fleni, Buenos Aires, Argentina
Claudia K. Suemoto
Division of Geriatrics, University of São Paulo Medical School, São Paulo, Brazil
Juan Fortea
Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Barcelona Down Medical Center, Fundació Catalana Síndrome de Down, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain
Pedro Rosa-Neto
Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Canada
Eduardo R. Zimmer
Brain Institute of Rio Grande do Sul, PUCRS, Porto Alegre, Brazil; Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil; Graduate Program in Biological Sciences, Biochemistry (PPGBioq), and Pharmacology and Therapeutics (PPGFT), Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil
Pamela C.L. Ferreira
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA
Bruna Bellaver
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA
Summary: Biomarkers have been instrumental in population selection and disease monitoring in clinical trials of recently FDA-approved drugs targeting amyloid-β to slow the progression of Alzheimer's disease (AD). As new therapeutic strategies and biomarker techniques emerge, the importance of biomarkers in drug development is growing exponentially. In this emerging landscape, biomarkers are expected to serve a wide range of contexts of use in clinical trials focusing on AD and related dementias. The joint FDA-NIH BEST (Biomarkers, EndpointS, and other Tools) framework provides standardised terminology to facilitate communication among stakeholders in this increasingly complex field. This review explores various applications of biomarkers relevant to AD clinical trials, using the BEST resource as a reference. For simplicity, we predominantly provide contextual characterizations of biomarkers use from the perspective of drugs targeting amyloid-β and tau proteins. However, general definitions and concepts can be extrapolated to other targets.
