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Chatterjee, M; Koel-Simmelink, MJ; Verberk, IM; Killestein, J; Vrenken, H; Enzinger, C; Ropele, S; Fazekas, F; Khalil, M; Teunissen, CE.
Contactin-1 and contactin-2 in cerebrospinal fluid as potential biomarkers for axonal domain dysfunction in multiple sclerosis.
Mult Scler J Exp Transl Clin. 2019; 4(4):2055217318819535-2055217318819535
Doi: 10.1177/2055217318819535
[OPEN ACCESS]
PubMed
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- Co-Autor*innen der Med Uni Graz
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Enzinger Christian
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Fazekas Franz
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Khalil Michael
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Ropele Stefan
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- Abstract:
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Contactin-1 and contactin-2 are important for the maintenance of axonal integrity.
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.
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.
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.
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.