Neurofilaments are elevated in the cerebrospinal fluid (CSF) and serum of ALS patients. However timing of this increase is unknown. To characterize the premanifest disease phase, we performed a cross-sectional study on asymptomatic (n=12) and symptomatic (n=64) ALS-mutation carriers and family controls (n=19). Neurofilaments NF-L and pNF-H are normal before symptom onset and increased by at least an order of magnitude at early symptom onset in CSF (pNF-H) or serum and CSF (NF-L). Thus blood and CSF neurofilament levels are linked to the symptomatic phase of ALS and might serve as objective markers of structural damage to the nervous system. This article is protected by copyright. All rights reserved.
