Contributions
Abstract: P1170
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Neuroaxonal damage and loss is the pathological substrate of permanent disability in various neurological disorders, including multiple sclerosis. Neurofilament light (NfL) protein is a marker to indicate such damage. Importantly, NfL levels can be measured not only in cerebrospinal fluid but also in a patient´s serum, which allows for repeated assessments. However, in order to correctly interpret serum NfL (sNfL) levels it is important to be able to compare individual patient measurements to reference values of healthy individuals (HD) and to know the range of variation of sNfL levels over time within the normal population.
Objective: To define age dependent reference values of sNfL in a single-centre cohort of HD both in a cross-sectional and longitudinal manner.
Methods: sNfL was measured by a single molecule array (Simoa) assay (Disanto et al., 2017). We analysed sNfL in 324(age range 38.5-85.6 years (y)) HD of the Austrian Stroke Prevention Study, which is a prospective community-based study on brain health and ageing in Graz, Austria. A follow-up serum sample was available in 96 HD (mean follow-up time 5.6 SD 1.0 y). All participants underwent detailed clinical examination, laboratory evaluation, cognitive testing, and brain MRI to exclude any significant comorbidity.
Results: Mean sNfL [pg/mL] levels below 60 y were 20.5 (SD 5.6) [40-50 y, n = 53] and 22.9 (SD 7.7) [50-60 y, n = 45] but then increased in a non-linear manner: 34.5 (SD 13.1) [60-70 y, n = 97]; 46.0 (SD 15.6) [>70 y, n =129]; regression analysis p < 0.0001, R2 = 0.42. The 95thpercentile cut-off sNfL [pg/mL] levels for the respective age ranges were 31.5, 34.7, 58.9 and 78.6. Using the Brown-Forsythe test we found a significant increase of group variances in sNfL levels above the age of 60 y (p < 0.0001). Using this age-dependent model, baseline sNfL values correctly predicted follow-up sNfL levels in 87.5%.
Conclusion: We here provide age dependent cut-off levels for sNfL in HD, which considerably increase in particular above the age of 60 together with an increasing standard deviation. This is probably due to an increasing number of individuals with sub-clinicallyinterfering pathology. On the other hand individual sNFL levels in the healthy appear to remain rather stable even over long time periods. Thisinformation should be helpful when using sNfL to identify and monitor neurologic disorders causing neuroaxonal damage.
Disclosure: Michael Khalil has received funding for travel and speaker honoraria from Bayer, Novartis, Merck, Biogen, Roche and Teva ratiopharm; serves on scientific advisory boards for Biogen and Roche and received a research grant from Teva ratiopharm.
Lukas Pirpamer declares that there is no conflict of interest.
Edith Hofer declares that there is no conflict of interest.
Margarete Voortman received funding from the Austrian Federal Ministry of Science, Research and Economics and was trained within the frame of the PhD Program Molecular Medicine of the Medical University of Graz.
Franz Hallwirth received funding from the Austrian Multiple Sclerosis Research Society and the Austrian Federal Ministry of Science, Research and Economics and was trained within the frame of the PhD Program Molecular Medicine of the Medical University of Graz.
Christian Barro received travel support by Teva and Novartis not related to this work.
Franz Fazekas serves on scientific advisory boards for Biogen Idec, Sanofi Genzyme, Merck, Novartis, Roche and Teva ratiopharm; serves on the editorial boards of the European Stroke Journal, Multiple Sclerosis Journal, Neurology, the Polish Journal of Neurology and Neurosurgery, and the Swiss Archives of Neurology and Psychiatry; provides consulting services for Actelion, Medday, Parexel and Teva ratiopharm and has received speaker honoraria from Merck, Genzyme-Sanofi and Teva ratiopharm.
Reinhold Schmidt declares that there is no conflict of interest related to this work.
Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
Abstract: P1170
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Neuroaxonal damage and loss is the pathological substrate of permanent disability in various neurological disorders, including multiple sclerosis. Neurofilament light (NfL) protein is a marker to indicate such damage. Importantly, NfL levels can be measured not only in cerebrospinal fluid but also in a patient´s serum, which allows for repeated assessments. However, in order to correctly interpret serum NfL (sNfL) levels it is important to be able to compare individual patient measurements to reference values of healthy individuals (HD) and to know the range of variation of sNfL levels over time within the normal population.
Objective: To define age dependent reference values of sNfL in a single-centre cohort of HD both in a cross-sectional and longitudinal manner.
Methods: sNfL was measured by a single molecule array (Simoa) assay (Disanto et al., 2017). We analysed sNfL in 324(age range 38.5-85.6 years (y)) HD of the Austrian Stroke Prevention Study, which is a prospective community-based study on brain health and ageing in Graz, Austria. A follow-up serum sample was available in 96 HD (mean follow-up time 5.6 SD 1.0 y). All participants underwent detailed clinical examination, laboratory evaluation, cognitive testing, and brain MRI to exclude any significant comorbidity.
Results: Mean sNfL [pg/mL] levels below 60 y were 20.5 (SD 5.6) [40-50 y, n = 53] and 22.9 (SD 7.7) [50-60 y, n = 45] but then increased in a non-linear manner: 34.5 (SD 13.1) [60-70 y, n = 97]; 46.0 (SD 15.6) [>70 y, n =129]; regression analysis p < 0.0001, R2 = 0.42. The 95thpercentile cut-off sNfL [pg/mL] levels for the respective age ranges were 31.5, 34.7, 58.9 and 78.6. Using the Brown-Forsythe test we found a significant increase of group variances in sNfL levels above the age of 60 y (p < 0.0001). Using this age-dependent model, baseline sNfL values correctly predicted follow-up sNfL levels in 87.5%.
Conclusion: We here provide age dependent cut-off levels for sNfL in HD, which considerably increase in particular above the age of 60 together with an increasing standard deviation. This is probably due to an increasing number of individuals with sub-clinicallyinterfering pathology. On the other hand individual sNFL levels in the healthy appear to remain rather stable even over long time periods. Thisinformation should be helpful when using sNfL to identify and monitor neurologic disorders causing neuroaxonal damage.
Disclosure: Michael Khalil has received funding for travel and speaker honoraria from Bayer, Novartis, Merck, Biogen, Roche and Teva ratiopharm; serves on scientific advisory boards for Biogen and Roche and received a research grant from Teva ratiopharm.
Lukas Pirpamer declares that there is no conflict of interest.
Edith Hofer declares that there is no conflict of interest.
Margarete Voortman received funding from the Austrian Federal Ministry of Science, Research and Economics and was trained within the frame of the PhD Program Molecular Medicine of the Medical University of Graz.
Franz Hallwirth received funding from the Austrian Multiple Sclerosis Research Society and the Austrian Federal Ministry of Science, Research and Economics and was trained within the frame of the PhD Program Molecular Medicine of the Medical University of Graz.
Christian Barro received travel support by Teva and Novartis not related to this work.
Franz Fazekas serves on scientific advisory boards for Biogen Idec, Sanofi Genzyme, Merck, Novartis, Roche and Teva ratiopharm; serves on the editorial boards of the European Stroke Journal, Multiple Sclerosis Journal, Neurology, the Polish Journal of Neurology and Neurosurgery, and the Swiss Archives of Neurology and Psychiatry; provides consulting services for Actelion, Medday, Parexel and Teva ratiopharm and has received speaker honoraria from Merck, Genzyme-Sanofi and Teva ratiopharm.
Reinhold Schmidt declares that there is no conflict of interest related to this work.
Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.