Axonal injury in asymptomatic individuals preceding onset of multiple sclerosis

Axonal loss is the main cause of irreversible disability in multiple sclerosis (MS). Serum neurofilament light (sNfL) is a biomarker of axonal disintegration. In this nested case-control study, blood samples from 519 presymptomatic persons (age range 4-39 years) who later received an MS diagnosis showed higher sNfL concentrations than 519 matched controls (p < 0.0001), noticeable at least 10 years before clinical MS onset. Mean values for pre-MS and control groups were 9.6 pg/mL versus 7.4 pg/mL 0-5 years before onset, and 6.4 pg/mL versus 5.8 pg/mL 5-10 years before onset. These results support that axonal injury occurs early in MS pathogenesis.
Funding Agencies|Swedish Government [ALFGBG-772071, ALFGBG-715986]; Swedish County Councils [ALFGBG-772071]; Research Foundation of the Gothenburg MS Society; Bjornsson Research Foundation, Gothenburg, Sweden; Gothenburg Society of Medicine; Swedish Research Council [2018-02532, 2017-00915]; European Research Council [681712]; Swedish State Support for Clinical Research [ALFGBG-720931]; Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862, RDAPB-201809-2016615]; AD Strategic Fund; Alzheimers Association [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C]; Olav Thon Foundation; Erling-Persson Family Foundation; Stiftelsen for Gamla Tjanarinnor, Hjarnfonden, Sweden [FO2019-0228]; European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [860197]; European Union Joint Program for Neurodegenerative Disorders [JPND2021-00694, JPND2019-466-236]; UK Dementia Research Institute at UCL; Swedish Alzheimer Foundation [AF-742881]; Hjarnfonden, Sweden [FO2017-0243]; Swedish County Councils, the ALFagreement [ALFGBG-715986]; National Institutes of Health (NIH), USA [1R01AG068398-01]; Alzheimers Association 2021 Zenith Award [ZEN-21-848495]