Fluid biomarkers in multiple sclerosis: from current to future applications

Abstract

Biomarkers; Cerebrospinal fluid; Multiple sclerosis

Biomarcadores; Líquido cefalorraquídeo; Esclerosis múltiple

Biomarcadors; Líquid cefaloraquidi; Esclerosi múltiple

Multiple sclerosis (MS) is an immune-mediated inflammatory and degenerative disorder of the central nervous system (CNS) with heterogeneous clinical manifestations. In the last decade, the landscape of cerebrospinal fluid (CSF) and blood biomarkers as potential key tools for MS diagnosis, prognosis and treatment monitoring has evolved considerably, alongside magnetic resonance imaging (MRI). CSF analysis has the potential not only to provide information on the underlying immunopathology of the disease and exclude differential diagnoses, but also to predict the risk of future relapses and disability accrual, guide therapeutic decisions and thus improve patient outcomes. This Series article overviews the biological framework and current applicability of fluid biomarkers for MS, exploring their potential role in the molecular characterisation of the disease. We discuss recent advances in the field of neurochemistry that enabled the detection of brain-derived proteins in blood, opening the door to much more efficient longitudinal disease monitoring. Furthermore, we identify the current challenges in the application of fluid biomarkers for MS in a real-world setting, while offering recommendations for harnessing their full potential as key paraclinical tools to improve patient management and personalise treatment.

Massimiliano Di Filippo receives support from the Ministero della Salute—Ricerca Finalizzata (RF-2021-12373319) and from Fondazione Italiana Sclerosi Multipla (FISM; project code 2023/PR-Single/017). Research of Charlotte E. Teunissen is supported by the European Commission (Marie Curie International Training Network, grant agreement No 860197 (MIRIADE), Innovative Medicines Initiatives 3 TR (Horizon 2020, grant no 831434) EPND (IMI 2 Joint Undertaking (JU), grant No. 101034344) and JPND (bPRIDE), National MS Society (Progressive MS alliance), Alzheimer's Drug Discovery Foundation, Alzheimer's Association, Health Holland, the Dutch Research Council (ZonMW), Alzheimer's Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Nederland. CT is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMw (#73305095007) and Health∼Holland, Top Sector Life Sciences & Health (PPP-allowance; #LSHM20106). Charlotte E. Teunissen is recipient of TAP-dementia, a ZonMw funded project (#10510032120003) in the context of the Dutch National Dementia Strategy. Luisa M Villar receives support from the Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER; “Otra manera de hacer Europa”) (Grants RD21/0002/0053 and grant PI21/00828) and, integrated in the Plan Estatal I + D + i, cofunded by Instituto de Salud Carlos III (ISCIII). She also receives funding from the European Commission (Innovative Medicines Initiatives 3 TR. Horizon 2020, grant no 831434). Henrik Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2023-00356; #2022-01018 and #2019–02397), the European Union’s Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer's Drug Discovery Foundation (ADDF), USA (#201809–2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C, and #ADSF-24-1284328-C), the Bluefield Project, Cure Alzheimer's Fund, the Olav Thon Foundation, the Erling-Persson Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme – Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003).