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Neurofilaments in pre-symptomatic ALS and the impact of genotype
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2019 (English)In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 20, no 7-8, p. 538-548Article in journal (Refereed) Published
Abstract [en]

Objective. To evaluate serum and cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy (pNfH), and to compare these to levels of neurofilament light (NfL), as biomarkers of pre-symptomatic ALS. Design. The study population includes 34 controls, 79 individuals at-risk for ALS, 22 ALS patients, and 14 phenoconverters. At-risk individuals are enrolled through Pre-Symptomatic Familial ALS (Pre-fALS), a longitudinal natural history and biomarker study of individuals who are carriers of any ALS-associated gene mutation, but who demonstrate no clinical evidence of disease at the time of enrollment. pNfH and NfL in serum and CSF were quantified using established enzyme-linked immunosorbent assays. Results. There is a longitudinal increase in serum pNfH in advance of the emergence of clinically manifest ALS. A similar pattern is observed for NfL, but with the absolute levels also frequently exceeding a normative threshold. Although CSF data are more sparse, similar patterns are observed for both neurofilaments, with absolute levels exceeding a normative threshold prior to phenoconversion. In serum, these changes are observed in the 6-12 months prior to disease among SOD1 A4V mutation carriers, and as far back as 2 and 3.5 years, respectively, in individuals with a FUS c.521del6 mutation and a C9ORF72 hexanucleotide repeat expansion. Conclusions. Serum and CSF pNfH increase prior to phenoconversion. In CSF, the temporal course of these changes is similar to NfL. In serum, however, pNfH is less sensitive to pre-symptomatic disease than NfL. The duration of pre-symptomatic disease, as defined by changes in neurofilaments, may vary depending on underlying genotype.

Place, publisher, year, edition, pages
Taylor & Francis, 2019. Vol. 20, no 7-8, p. 538-548
Keywords [en]
Amyotrophic lateral sclerosis, neurofilaments, biomarkers, pre-symptomatic, disease prevention
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:umu:diva-163682DOI: 10.1080/21678421.2019.1646769ISI: 000482522900001PubMedID: 30892087OAI: oai:DiVA.org:umu-163682DiVA, id: diva2:1362801
Available from: 2019-10-21 Created: 2019-10-21 Last updated: 2019-10-21Bibliographically approved

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Andersen, Peter M.

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Department of Pharmacology and Clinical Neuroscience
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