title: N-acetylaspartate and neurofilaments as biomarkers of axonal damage in patients with progressive forms of multiple sclerosis.
abstract: Primary and secondary progressive forms of multiple sclerosis (PPMS and SPMS) have different pathological characteristics. However, it is unknown whether neurodegenerative mechanisms are shared. We measured cerebrospinal fluid (CSF) levels of neurofilament (Nf) light and heavy isoforms and N-acetylaspartic acid (NAA) in 21 PP, 10 SPMS patients and 15 non-inflammatory neurological disease controls (NINDC). Biomarkers were related to Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) over a long period of follow-up [median (interquartile range) 9 (5.5-12.5) years] in 19 PPMS and 4 SPMS patients, and to T2 lesion load, T1 lesion load, and brain parenchymal fraction at the time of lumbar puncture. Nf light was higher in PPMS (p < 0.005) and Nf heavy was increased in both SPMS and PPMS (p < 0.05 and p < 0.01) compared to NINDC, but were comparable between the two MS subtypes. Nf heavy was a predictor of the ongoing disability measured by MSSS (R(2) = 0.17, β = 0.413; p < 0.05). Conversely, Nf light was the only predictor of the EDSS annual increase (R(2) = 0.195, β = 0.441; p < 0.05). The frequency of abnormal biomarkers did not differ between the two MS progressive subtypes. Our data suggest that PP and SPMS likely share similar mechanisms of axonal damage. Moreover, Nf heavy can be a biomarker of ongoing axonal damage. Conversely, Nf light can be used as a prognostic marker for accumulating disability suggesting it as a good tool for possible treatment monitoring in the progressive MS forms.
authors.affiliation: Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre (VUMC), Amsterdam, The Netherlands, alessandro.trentini@unife.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Trentini
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella
authors.forename: Mar
authors.initials: M
authors.lastname: Tintoré
authors.forename: Marleen J A
authors.initials: MJ
authors.lastname: Koel-Simmelink
authors.forename: Joep
authors.initials: J
authors.lastname: Killestein
authors.forename: Birthe
authors.initials: B
authors.lastname: Roos
authors.forename: Alex
authors.initials: A
authors.lastname: Rovira
authors.forename: Carsten
authors.initials: C
authors.lastname: Korth
authors.forename: Philipp
authors.initials: P
authors.lastname: Ottis
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bellini
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid; D001369:Axons / Q000473:pathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000473:pathology*; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D011379:Prognosis
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins; D001224:Aspartic Acid; C000179:N-acetylaspartate