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Publication
Alzheimer's Research and Therapy

Fluid biomarkers for neurodegenerative diseases: a comprehensive update

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  • December 20, 2025
  • Aitana Sogorb-Esteve, et al., UCL
Topic/Product:
CNS Disease Panel 120, Technology
Disease Area:
Neurodevelopmental Disabilities (NDD)
Sample Type:

Abstract

Fluid biomarkers are revolutionizing the diagnosis and management of neurodegenerative diseases by enabling earlier diagnosis and disease monitoring. In particular, blood-based biomarkers have emerged as a minimally invasive and scalable alternative to cerebrospinal fluid analysis. Recent advances in blood-based tau biomarkers have shown high diagnostic accuracy for Alzheimer’s disease (AD). Other neurodegenerative diseases—such as synucleinopathies, frontotemporal lobar degeneration, limbic-predominant age-related TDP-43 encephalopathy (LATE), and amyotrophic lateral sclerosis—pose substantial challenges due to their heterogeneous clinical presentations and the current absence of robust biomarkers for hallmark pathologies. Nonetheless, promising candidate markers are emerging for improved disease characterization and staging. Technological innovations, including single-molecule arrays (Simoa), advanced mass spectrometry workflows and nucleic acid linked immune-sandwich assay (NULISA) have markedly enhanced the sensitivity and precision of biomarker quantification from low-concentration biological matrices. More recently, the development of fully automated platforms shows great promise for routine measurement of blood-based biomarkers in clinical settings. Despite this progress key challenges remain, including the need for improved assay reproducibility, standardization, and the optimization of clinical workflows. In this review, we provide a comprehensive update on recent progress in fluid biomarker research across AD and major neurodegenerative diseases, highlight technological advances in detection methods, and discuss current challenges and opportunities for clinical translation.

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Authors & Affiliations

Martina Valletta¹*, Nils Briel²³*, Idil Yuksekel⁴, Michelle Barboure⁵⁶, Anna Coward⁷⁸⁹, Julie F. H. De Houwer¹⁰, Ayesha Fawad¹¹, Alberto González-Mayoral⁴, Gianmarco Iaccarino⁷¹², Francisco Martínez-Dubarbie¹³¹⁴¹⁵, Shirine Moukaled¹⁶, Ulf Andreasson¹⁷¹⁸, Johan Gobom¹⁷¹⁸, Ann Brinkmalm¹⁷¹⁸, Betty Tijms⁵⁶, Henrik Zetterberg¹⁷¹⁸¹⁹²⁰²¹²², Kaj Blennow¹⁷¹⁸²³²⁴, Marc Suárez-Calvet⁷¹²²⁵, Michael Schöll¹⁷²⁶²⁷²⁸, Ross W. Paterson¹⁹, Laia Montoliu-Gaya¹⁷#, and Aitana Sogorb-Esteve²⁷²⁹#

¹ Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
² Department of Neurology, University Hospital Zurich, Zurich, Switzerland
³ Zurich Neuroscience Center, University of Zurich, Zurich, Switzerland
⁴ Paris Brain Institute, Sorbonne Université, INSERM U1127, CNRS 7225, Hôpital Pitié-Salpêtrière, Paris, France
⁵ Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands
⁶ Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands
⁷ Barcelona Beta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain
⁸ Centro de Investigación Biomédica en Red – Fragilidad y Envejecimiento Saludable (CIBER-FES), Madrid, Spain
⁹ Universitat Autònoma de Barcelona, Barcelona, Spain
¹⁰ Department of Neurology and Alzheimer Centre, Erasmus MC University Medical Centre, Rotterdam, the Netherlands
¹¹ Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden
¹² Hospital del Mar Research Institute, Barcelona, Spain
¹³ Neurology Service, Marqués de Valdecilla University Hospital, Santander, Cantabria, Spain
¹⁴ Institute for Research Marqués de Valdecilla (IDIVAL), Santander, Cantabria, Spain
¹⁵ CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, Instituto de Salud Carlos III, Madrid, Spain
¹⁶ Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA
¹⁷ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
¹⁸ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
¹⁹ Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK
²⁰ UK Dementia Research Institute, University College London, London, UK
²¹ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China
²² UW Department of Medicine, School of Medicine and Public Health, Madison, WI, USA
²³ Paris Brain Institute (ICM), Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
²⁴ Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, China
²⁵ Servei de Neurologia, Hospital del Mar, Barcelona, Spain
²⁶ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
²⁷ Dementia Research Centre, Queen Square Institute of Neurology, University College London, London, UK
²⁸ Department of Psychiatry, Cognition and Aging Psychiatry, Sahlgrenska University Hospital, Mölndal, Sweden
²⁹ UK Dementia Research Institute at University College London, London, UK

* contributed equally
# contributed equally

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Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

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Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.