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CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival
Skillbäck T, Farahmand B, Bartlett JW, Rosén C, Mattsson N, Nägga K, Kilander L, Religa D et al.. Neurology, 2014-10-22
Topic: Brain proteins, microglia and lab models
Objectives We hypothesized that CSF neurofilament light (NFL) levels would be elevated in dementias with subcortical involvement, including vascular dementia (VaD), but less elevated in dementias primarily affecting gray matter structures, such as Alzheimer disease (AD), and that elevated CSF NFL would correlate with disease severity and shorter survival time irrespective of clinical diagnosis. Methods We included 3,356 individuals with dementia who had CSF NFL analyzed in our laboratory between 2005 and 2012. Clinical diagnoses and Mini-Mental State Examination (MMSE) scores were obtained from the Swedish Dementia Registry, and in selected cases (n = 478), date of death from the Swedish Mortality Registry. Results CSF NFL differed among clinical diagnoses, with the highest levels seen in frontotemporal dementia, VaD, and mixed AD and VaD. Early-onset AD (younger than 65 years) had the lowest levels. High CSF NFL correlated with low MMSE score and short survival time irrespective of diagnosis, and was also particularly evident in AD. Conclusions CSF NFL differs among different neurodegenerative diseases and is especially high in dementias engaging subcortical brain regions, such as VaD and mixed AD and VaD, but also in frontotemporal dementia. The association of high CSF NFL levels with disease severity and short survival supports the notion that high CSF NFL levels indicate more aggressive disease processes.
Key findings
- Results CSF NFL differed among clinical diagnoses, with the highest levels seen in frontotemporal dementia, VaD, and mixed AD and VaD.
Why it matters
In 3,356 people with dementia in Swedish registries, spinal-fluid neurofilament light (NFL) was highest in frontotemporal dementia, vascular dementia and mixed Alzheimer's/vascular dementia, and lowest in Alzheimer's that began before 65. Across all diagnoses, and particularly in Alzheimer's, higher NFL went with lower MMSE scores and, in a subset of 478 people, shorter survival. The authors say this supports high NFL as a sign of more aggressive disease; it is a correlation, not a diagnostic test for Alzheimer's or a treatment.
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Study details
- Participants478
- Evidence strengthLow
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 478 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 263 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.8 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 12.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 21 other studies in this library |
| Still being cited | 2 / 4 | Cited 38 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Henrik Zetterberg: h-index 196 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25339208) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
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May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Skillbäck, T., Farahmand, B., Bartlett, J. W., Rosén, C., Mattsson, N., Nägga, K., et al. (2014). CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival. Neurology. https://doi.org/10.1212/wnl.0000000000001015
Vancouver
Skillbäck T, Farahmand B, Bartlett JW, Rosén C, Mattsson N, Nägga K, et al. CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival. Neurology. 2014. doi:10.1212/wnl.0000000000001015. PMID: 25339208.
BibTeX
@article{skillback2014-25339208,
author = {Skillbäck, T. and Farahmand, B. and Bartlett, J. W. and Rosén, C. and Mattsson, N. and Nägga, K. and Kilander, L. and Religa, D. and others},
title = {{CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival}},
journal = {Neurology},
year = {2014},
doi = {10.1212/wnl.0000000000001015},
pmid = {25339208},
url = {https://doi.org/10.1212/wnl.0000000000001015}
}
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