REVIEW Open Access Perspectives in fluid biomarkers in neurodegeneration from the 2019 biomarkers in neurodegenerative diseases course—a joint PhD student course at University College London and University of Gothenburg Pawel Obrocki 1* , Ayesha Khatun 2 , Deborah Ness 3 , Konstantin Senkevich 4,5 , Jörg Hanrieder 6,7 , Federica Capraro 8,9 , Niklas Mattsson 10,11 , Ulf Andreasson 7,12 , Erik Portelius 7,12 , Nicholas J. Ashton 7,13,14,15 , Kaj Blennow 7,12 , Michael Schöll 2,7,13,16 , Ross W. Paterson 2 , Jonathan M. Schott 2† and Henrik Zetterberg 7,12,17,18† Abstract Until relatively recently, a diagnosis of probable Alzheimer’s disease (AD) and other neurodegenerative disorders was principally based on clinical presentation, with post-mortem examination remaining a gold standard for disease confirmation. This is in sharp contrast to other areas of medicine, where fluid biomarkers, such as troponin levels in myocardial infarction, form an integral part of the diagnostic and treatment criteria. There is a pressing need for such quantifiable and easily accessible tools in neurodegenerative diseases. In this paper, based on lectures given at the 2019 Biomarkers in Neurodegenerative Diseases Course, we provide an overview of a range of cerebrospinal fluid (CSF) and blood biomarkers in neurodegenerative disorders, including the ‘core’ AD biomarkers amyloid β (Aβ) and tau, as well as other disease-specific and general markers of neuroaxonal injury. We then highlight the main challenges in the field, and how those could be overcome with the aid of new methodological advances, such as assay automation, mass spectrometry and ultrasensitive immunoassays. As we hopefully move towards an era of disease-modifying treatments, reliable biomarkers will be essential to increase diagnostic accuracy, allow for earlier diagnosis, better participant selection and disease activity and treatment effect monitoring. Keywords: Biomarkers, Neurodegeneration, Amyloid, Tau, Neurofilament light, Neurogranin, α-Synuclein, ELISA, Simoa, Mass spectrometry © The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. * Correspondence: pawel.obrocki@nhs.net † Jonathan M. Schott and Henrik Zetterberg contributed equally to this work. 1 Department of Medicine, St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK Full list of author information is available at the end of the article Obrocki et al. Alzheimer's Research & Therapy (2020) 12:20 https://doi.org/10.1186/s13195-020-00586-6