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Publications

Journal Article Ppublish

PubMed: 40414160 DOI: 10.1016/j.ebiom.2025.105741

A plasma biomarker panel for detecting early amyloid-β accumulation and its changes in middle-aged cognitively unimpaired individuals at risk for Alzheimer's disease.

EBioMedicine 116:105741

Authors: Armand González-Escalante, Marta Milà-Alomà, Wagner S Brum, Nicholas J Ashton, Paula Ortiz-Romero, Mahnaz Shekari, Marta Del Campo, Federica Anastasi, Clara Quijano-Rubio, Gwendlyn Kollmorgen, Carolina Minguillón, Gonzalo Sánchez-Benavides, Oriol Grau-Rivera, Juan Domingo Gispert, Henrik Zetterberg, Natalia Vilor-Tejedor, Kaj Blennow, Marc Suárez-Calvet

Affiliations

  • Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Hospital del Mar Research Institute, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain.
  • Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States of America; Department of Veterans Affairs Medical Center, Northern California Institute for Research and Education (NCIRE), San Francisco, CA, United States of America.
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, United Kingdom; Banner Alzheimer's Institute and University of Arizona, Phoenix, AZ, United States of America; Banner Sun Health Research Institute, Sun City, AZ, United States of America.
  • Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Hospital del Mar Research Institute, Barcelona, Spain.
  • Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Hospital del Mar Research Institute, Barcelona, Spain; Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • Roche Diagnostics International Ltd, Rotkreuz, Switzerland.
  • Roche Diagnostics GmbH, Penzberg, Germany.
  • Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Hospital del Mar Research Institute, Barcelona, Spain; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain.
  • Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Hospital del Mar Research Institute, Barcelona, Spain; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain; Servei de Neurologia, Hospital del Mar, Barcelona, Spain.
  • Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Hospital del Mar Research Institute, Barcelona, Spain; Centro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, United Kingdom; UK Dementia Research Institute, University College London, London, United Kingdom; Hong Kong Center for Neurodegenerative Diseases (HKCeND), Hong Kong, China; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States of America.
  • Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Hospital del Mar Research Institute, Barcelona, Spain; Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Department of Genetics, Radboud University Nijmegen, Nijmegen, Netherlands.
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France; Division of Life Sciences and Medicine and Department of Neurology, Neurodegenerative Disorder Research Center, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, PR China.
  • Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Hospital del Mar Research Institute, Barcelona, Spain; Servei de Neurologia, Hospital del Mar, Barcelona, Spain.

Abstract

BACKGROUND

Plasma biomarkers of Alzheimer's disease (AD) change during preclinical stages, indicating potential for detecting amyloid-β (Aβ) pathology in cognitively unimpaired (CU) individuals. Given the need for accurate, scalable biomarkers, we evaluated a fully automated plasma panel to detect and monitor longitudinal Aβ accumulation in CU individuals.

METHODS

In this longitudinal study, we examined a plasma panel (Aβ42/40, p-tau181, GFAP, NfL, p-tau217 and ApoE4) in CU participants at risk for AD. We assessed the biomarkers' performance to detect Aβ pathology and the cross-sectional and longitudinal relationships between the biomarkers and Aβ accumulation, neurodegeneration and cognition.

FINDINGS

We included 400 middle-aged CU participants, of whom 135 (33.8%) were CSF Aβ-positive. All plasma biomarkers differed between Aβ-positive and -negative individuals, with plasma Aβ42/40, p-tau217, p-tau181/Aβ42, and p-tau217/Aβ42 showing the best performance in detecting A+ CU individuals. However, plasma Aβ42/40 was sensitive to random variability. Plasma p-tau217/Aβ42 had the highest performance in detecting PET A+ individuals (AUC = 0.94). All baseline plasma biomarkers were associated with longitudinal increases in Aβ deposition (mean follow-up [SD]: 3.27 ± 0.5). Longitudinal changes in plasma p-tau217 and p-tau217/Aβ42 were associated with concurrent changes in Aβ (both CSF and PET) and soluble tau pathology.

INTERPRETATION

In CU individuals, several plasma biomarkers at baseline detect Aβ accumulation and are associated with its short-term change. Plasma p-tau217, and p-tau217/Aβ42 longitudinal changes reflect concurrent Aβ accumulation during this period. These findings help enrich studies in CU individuals at risk of progressing to AD.

FUNDING

ERC-2020-STG (Grant agreement No. 948677); ERA PerMed-ERA NET and the Generalitat de Catalunya (SLD077/21/000001); PI19/00155; PI22/00456, LCF/BQ/PR21/11840004.

MeSH

Alzheimer Disease, Biomedical Research, Pathology, Biomarkers, Aged, Amyloid, Plasma