TY - JOUR
T1 - Contactin-1 and contactin-2 in cerebrospinal fluid as potential biomarkers for axonal domain dysfunction in multiple sclerosis
AU - Chatterjee, Madhurima
AU - Koel-Simmelink, Marleen J.A.
AU - Verberk, Inge M.W.
AU - Killestein, Joep
AU - Vrenken, Hugo
AU - Enzinger, Christian
AU - Ropele, Stefan
AU - Fazekas, Franz
AU - Khalil, Michael
AU - Teunissen, Charlotte E.
N1 - Publisher Copyright: © The Author(s) 2018.
PY - 2018
Y1 - 2018
N2 - Background: Contactin-1 and contactin-2 are important for the maintenance of axonal integrity. Objective: To investigate the cerebrospinal fluid levels of contactin-1 and contactin-2 in multiple sclerosis patients and controls, and their potential use as prognostic markers for neurodegeneration. Methods: Cerebrospinal fluid contactin-1 and contactin-2 were measured in relapsing–remitting multiple sclerosis (n = 41), secondary progressive multiple sclerosis (n = 26) and primary progressive multiple sclerosis patients (n = 13) and controls (n = 18), and in a second cohort with clinically isolated syndrome patients (n = 88, median clinical follow-up period of 2.3 years) and controls (n = 20). Correlations/linear regressions were analysed with other baseline cerebrospinal fluid axonal damage markers and cross-sectional/longitudinal magnetic resonance imaging features. Results: Contactin-1 and contactin-2 levels were up to 1.4-fold reduced in relapsing–remitting multiple sclerosis (contactin-1: p = 0.01, contactin-2: p = 0.02) and secondary progressive multiple sclerosis (contactin-1: p = 0.05, contactin-2: p = 0.02) compared to controls. In clinically isolated syndrome patients, contactin-1 tended to increase when compared to controls (p = 0.07). Both contactin-1 and contactin-2 correlated with neurofilament light, neurofilament heavy and magnetic resonance imaging metrics differently depending on the disease stage. In clinically isolated syndrome patients, baseline contactin-2 level (β = –0.42, p = 0.04) predicted the longitudinal decline in cortex volume. Conclusion: Cerebrospinal fluid contactin-1 and contactin-2 reveal axonal dysfunction in various stages of multiple sclerosis and their inclusion to the biomarker panel may provide better insight into the extent of axonal damage/dysfunction.
AB - Background: Contactin-1 and contactin-2 are important for the maintenance of axonal integrity. Objective: To investigate the cerebrospinal fluid levels of contactin-1 and contactin-2 in multiple sclerosis patients and controls, and their potential use as prognostic markers for neurodegeneration. Methods: Cerebrospinal fluid contactin-1 and contactin-2 were measured in relapsing–remitting multiple sclerosis (n = 41), secondary progressive multiple sclerosis (n = 26) and primary progressive multiple sclerosis patients (n = 13) and controls (n = 18), and in a second cohort with clinically isolated syndrome patients (n = 88, median clinical follow-up period of 2.3 years) and controls (n = 20). Correlations/linear regressions were analysed with other baseline cerebrospinal fluid axonal damage markers and cross-sectional/longitudinal magnetic resonance imaging features. Results: Contactin-1 and contactin-2 levels were up to 1.4-fold reduced in relapsing–remitting multiple sclerosis (contactin-1: p = 0.01, contactin-2: p = 0.02) and secondary progressive multiple sclerosis (contactin-1: p = 0.05, contactin-2: p = 0.02) compared to controls. In clinically isolated syndrome patients, contactin-1 tended to increase when compared to controls (p = 0.07). Both contactin-1 and contactin-2 correlated with neurofilament light, neurofilament heavy and magnetic resonance imaging metrics differently depending on the disease stage. In clinically isolated syndrome patients, baseline contactin-2 level (β = –0.42, p = 0.04) predicted the longitudinal decline in cortex volume. Conclusion: Cerebrospinal fluid contactin-1 and contactin-2 reveal axonal dysfunction in various stages of multiple sclerosis and their inclusion to the biomarker panel may provide better insight into the extent of axonal damage/dysfunction.
KW - CSF biomarker
KW - Contactin
KW - axonal damage
KW - multiple sclerosis
KW - neurofilament
UR - http://www.scopus.com/inward/record.url?scp=85085081750&partnerID=8YFLogxK
U2 - https://doi.org/10.1177/2055217318819535
DO - https://doi.org/10.1177/2055217318819535
M3 - Article
C2 - 30627437
SN - 2055-2173
VL - 4
JO - Multiple sclerosis journal - experimental, translational and clinical
JF - Multiple sclerosis journal - experimental, translational and clinical
IS - 4
ER -