TY - JOUR
T1 - Neuroaxonal and Glial Markers in Patients of the Same Age With Multiple Sclerosis
AU - Loonstra, Floor C
AU - de Ruiter, Lodewijk R J
AU - Koel-Simmelink, Marleen J A
AU - Schoonheim, Menno M
AU - Strijbis, Eva M M
AU - Moraal, Bastiaan
AU - Barkhof, Frederik
AU - Uitdehaag, Bernard M J
AU - Teunissen, Charlotte
AU - Killestein, Joep
N1 - Funding Information: This study was supported by the VriendenLoterij, Dutch MS Research Foundation, Mission Summit, and VUmc Foundation. Funding Information: F.C. Loonstra, L.R.J. de Ruiter, B. Moraal, and E.M. Strijbis report no competing interests. M.M. Schoonheim serves on the editorial board of Neurology and Frontiers in Neurology, receives research support from the Dutch MS Research Foundation and Amsterdam Neuroscience, and has served as a consultant for or received research support and/or speaker honoraria from Atara Biotherapeutics, Biogen, Celgene, Genzyme, MedDay, and Merck. F. Barkhof: steering committee and iDMC member for Biogen, Merck, Roche, and EISAI; Consultant for Roche, Biogen, Merck, IXICO, Jansen, Combinostics. Research agreements with Novartis, Merck, Biogen, GE, Roche. Co-founder and shareholder of Queen Square Analytics LTD. B.M.J. Uitdehaag received consultancy fees from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, and Teva and Immunic Therapeutics. C. Teunissen has served on advisory boards for Roche, has received nonfinancial support in the form of research consumables from ADx NeuroSciences and Euroimmun, and has performed contract research or received grants from Probiodrug, Biogen, Esai, Toyama, Janssen Prevention Center, Boehringer, Axon Neuroscience, EIP Pharma, PeopleBio, Qunaterix, and Roche. J. Killestein has speaker relationships with Biogen, Genzyme, Merck, Novartis, Roche, Sanofi, and TEVA. Go to Neurology.org/NN for full disclosures. Publisher Copyright: © American Academy of Neurology.
PY - 2023/3/21
Y1 - 2023/3/21
N2 - BACKGROUND AND OBJECTIVES: The specificity of novel blood biomarkers for multiple sclerosis (MS)-related neurodegeneration is unclear because neurodegeneration also occurs during normal aging. To understand which aspects of neurodegeneration the serum biomarkers neurofilament light (sNfL), serum glial fibrillary acidic protein (sGFAP), and serum contactin-1 (sCNTN1) reflect, we here explore their cross-sectional association with disability outcome measures and MRI volumes in a unique cohort of people with MS (PwMS) of the same age. METHODS: sNfL, sGFAP (both singe-molecule array technology) and sCNTN1 (Luminex) were measured in serum samples of 288 PwMS and 125 healthy controls (HCs) of the Project Y cohort, a population-based cross-sectional study of PwMS born in the Netherlands in 1966 and age-matched HC. RESULTS: sNfL (9.83 pg/mL [interquartile range {IQR}: 7.8-12.0]) and sGFAP (63.7 pg/mL [IQR: 48.5-84.5]) were higher in PwMS compared with HC (sNfL: 8.8 pg/mL [IQR: 7.0-10.5]; sGFAP: 51.7 pg/mL [IQR: 40.1-68.3]) (p < 0.001), whereas contactin-1 (7,461.3 pg/mL [IQR: 5,951.8-9,488.6]) did not significantly differ between PwMS compared with HC (7,891.2 pg/mL [IQR: 6,120.0-10,265.8]) (p = 0.068). sNfL and sGFAP levels were 1.2-fold higher in secondary progressive patients (SPMS) compared with relapsing remitting patients (p = 0.009 and p = 0.043). Stratified by MS subtype, no relations were seen for CNTN1, whereas sNfL and sGFAP correlated with the Expanded Disability Status Scale (ρ = 0.43 and ρ = 0.39), Nine-Hole Peg Test, Timed 25-Foot Walk Test, and Symbol Digit Modalities Test (average ρ = 0.38) only in patients with SPMS. Parallel to these clinical findings, correlations were only found for sNfL and sGFAP with MRI volumes. The strongest correlations were observed between sNfL and thalamic volume (ρ = -0.52) and between sGFAP with deep gray matter volume (ρ = - 0.56) in primary progressive patients. DISCUSSION: In our cohort of patients of the same age, we report consistent correlations of sNfL and sGFAP with a range of metrics, especially in progressive MS, whereas contactin-1 was not related to clinical or MRI measures. This demonstrates the potential of sNfL and sGFAP as complementary biomarkers of neurodegeneration, reflected by disability, in progressive MS.
AB - BACKGROUND AND OBJECTIVES: The specificity of novel blood biomarkers for multiple sclerosis (MS)-related neurodegeneration is unclear because neurodegeneration also occurs during normal aging. To understand which aspects of neurodegeneration the serum biomarkers neurofilament light (sNfL), serum glial fibrillary acidic protein (sGFAP), and serum contactin-1 (sCNTN1) reflect, we here explore their cross-sectional association with disability outcome measures and MRI volumes in a unique cohort of people with MS (PwMS) of the same age. METHODS: sNfL, sGFAP (both singe-molecule array technology) and sCNTN1 (Luminex) were measured in serum samples of 288 PwMS and 125 healthy controls (HCs) of the Project Y cohort, a population-based cross-sectional study of PwMS born in the Netherlands in 1966 and age-matched HC. RESULTS: sNfL (9.83 pg/mL [interquartile range {IQR}: 7.8-12.0]) and sGFAP (63.7 pg/mL [IQR: 48.5-84.5]) were higher in PwMS compared with HC (sNfL: 8.8 pg/mL [IQR: 7.0-10.5]; sGFAP: 51.7 pg/mL [IQR: 40.1-68.3]) (p < 0.001), whereas contactin-1 (7,461.3 pg/mL [IQR: 5,951.8-9,488.6]) did not significantly differ between PwMS compared with HC (7,891.2 pg/mL [IQR: 6,120.0-10,265.8]) (p = 0.068). sNfL and sGFAP levels were 1.2-fold higher in secondary progressive patients (SPMS) compared with relapsing remitting patients (p = 0.009 and p = 0.043). Stratified by MS subtype, no relations were seen for CNTN1, whereas sNfL and sGFAP correlated with the Expanded Disability Status Scale (ρ = 0.43 and ρ = 0.39), Nine-Hole Peg Test, Timed 25-Foot Walk Test, and Symbol Digit Modalities Test (average ρ = 0.38) only in patients with SPMS. Parallel to these clinical findings, correlations were only found for sNfL and sGFAP with MRI volumes. The strongest correlations were observed between sNfL and thalamic volume (ρ = -0.52) and between sGFAP with deep gray matter volume (ρ = - 0.56) in primary progressive patients. DISCUSSION: In our cohort of patients of the same age, we report consistent correlations of sNfL and sGFAP with a range of metrics, especially in progressive MS, whereas contactin-1 was not related to clinical or MRI measures. This demonstrates the potential of sNfL and sGFAP as complementary biomarkers of neurodegeneration, reflected by disability, in progressive MS.
KW - Biomarkers
KW - Contactins
KW - Cross-Sectional Studies
KW - Humans
KW - Multiple Sclerosis, Chronic Progressive/diagnostic imaging
KW - Multiple Sclerosis/diagnostic imaging
KW - Neurofilament Proteins
UR - http://www.scopus.com/inward/record.url?scp=85144590980&partnerID=8YFLogxK
U2 - https://doi.org/10.1212/NXI.0000000000200078
DO - https://doi.org/10.1212/NXI.0000000000200078
M3 - Article
C2 - 36543540
SN - 2332-7812
VL - 10
JO - Neurology(R) neuroimmunology & neuroinflammation
JF - Neurology(R) neuroimmunology & neuroinflammation
IS - 2
M1 - e200078
ER -