Reference interval and preanalytical properties of serum neurofilament light chain in Scandinavian adults
Abstract
The neurofilament light chain (NfL) is a promising biomarker of neuronal injury which is approaching routine clinical use. With the development of ultra-sensitive technologies, NfL has become measurable in the peripheral blood but the reference interval for serum NfL remains to be established. NfL was measured by a single-molecule array (Simoa™) analysis under internal and external quality control which is established for routine clinical use. Serum samples from 342 reference subjects, 18-87 years were analyzed. The age-partitioned reference interval was established according to Clinical and Laboratory Standards Institute guidelines, an approximation of the upper reference interval limit per 10-year age-groups was performed, and key pre-analytical properties were examined. Serum NfL levels increased 2.9% per year. The non-parametric reference interval for the age groups 18-40, 41-65, and >65 years were 2.8-9.7 ng/L, 4.6 - 21.4 ng/L, and 7.5-53.8 ng/L, respectively. The estimated upper reference interval limits per 10-year intervals corresponded well with the 90% confidence limits of the non-parametric reference interval. The recovery of serum NfL after seven days at room temperature or three freeze-thaw cycles were 93% (95% CI: 89%-97%) and 92% (95% CI: 83%-102%) and levels in serum were only slightly higher than levels in plasma ( p < .0001). The study establishes the serum NfL reference interval, provide estimated upper reference intevral limits in 10-year intervals to incr…
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The mean concentration of NfL in plasma was 10% lower (95% CI 5-16) than in serum.
“First, the mean concentration of NfL in plasma was 10% lower (95% CI 5–16) than in serum which compares well to another investigation10.”
From Seven day pre-analytical stability of serum and plasma neurofilament light chain (2021) · cites this paper as [10]
Our results are in line with two other studies reporting pre-analytical stability of serum NfL in smaller cohorts, making this the largest study confirming this observation for both serum and plasma.
“Our results are in line with two other studies reporting pre-analytical stability of serum NfL in smaller cohorts making this the largest study confirming this observation for both serum and plasma10,11.”
From Seven day pre-analytical stability of serum and plasma neurofilament light chain (2021) · cites this paper as [10]
Some studies report median differences between serum and plasma NfL and GFAP.
“Some studies report median differences,15–18 and only one has proposed a serum–plasma conversion for NfL in older adults, 19 with none for GFAP.”
From Establishing demographic-based normative values for neurofilament light chain and glial fibrillary acidic protein in serum and plasma samples (2026) · cites this paper as [18]
In those four studies, strengths of correlation were tested via Spearman's correlation coefficient.
“In all studies, however, strengths of correlation were tested via Spearman's correlation coefficient.”
From A Method to Combine Neurofilament Light Measurements From Blood Serum and Plasma in Clinical and Population-Based Studies (2022) · cites this paper as [16]
Four studies consistently reported higher NfL levels in serum than in plasma.
“They consistently reported higher NfL levels in serum than in plasma.”
From A Method to Combine Neurofilament Light Measurements From Blood Serum and Plasma in Clinical and Population-Based Studies (2022) · cites this paper as [16]
We confirm the numerical differences between serum and EDTA-plasma NfL levels that have been found in other studies.
“We confirm the numerical differences between serum and EDTA-plasma NfL levels that have been found in other studies (15–18).”
From A Method to Combine Neurofilament Light Measurements From Blood Serum and Plasma in Clinical and Population-Based Studies (2022) · cites this paper as [16]
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Neurofilament light chain: a biomarker for genetic frontotemporal dementia
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Blood neurofilament light: a critical review of its application to neurologic disease
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Seven day pre-analytical stability of serum and plasma neurofilament light chain
Altmann, P., Ponleitner, M., Rommer, P. S., Haslacher, H., Mucher, P., Leutmezer, F., Petzold, A., Wotawa, C., Lanzenberger, R., Berger, T., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-90639-z · Cited by 68 · see citing works
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- Authors
- Hviid, C. V. B., Knudsen, C. S., & Parkner, T.
- Affiliations
- Aarhus University Hospital (DK)
- Corresponding author
- Hviid, Claus Vinter Bødker
- Venue
- Scandinavian Journal of Clinical and Laboratory Investigation
- Publisher
- Informa UK Limited
- Published
- 2020-02-20
- Volume
- 80
- Issue
- 4
- Pages
- 291-295
- ISSN
- 0036-5513 (ISSN-L)
- 1502-7686
- OpenAlex
- W3008567086
- Cited by
- 143
- References
- 2
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 23 · 2023: 31 · 2022: 26 · 2021: 15 · 2020: 9
- FWCI
- 12.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Scandinavian Journal of Clinical and Laboratory Investigation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced Biosensing Techniques and Applications
- Keywords
- serum neurofilament light chain, reference values, Simoa single molecule array, freeze-thaw stability
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Nerve Tissue, Reference Values, Scandinavian and Nordic Countries, Biomarkers, Neurofilament Proteins, Healthy Volunteers
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