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Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration
Scherling CS, Hall T, Berisha F, Klepac K, Karydas A, Coppola G, Kramer JH, Rabinovici G et al.. Annals of neurology, 2014-01-02
Topic: Brain proteins, microglia and lab models
Objective Cerebrospinal fluid (CSF) neurofilament light chain (NfL) concentration is elevated in neurological disorders, including frontotemporal degeneration (FTD). We investigated the clinical correlates of elevated CSF NfL levels in FTD. Methods CSF NfL, amyloid-β1-42 (Aβ42), tau, and phosphorylated tau concentrations were compared in 47 normal controls (NC), 8 asymptomatic gene carriers (NC2) of FTD-causing mutations, and 79 FTD (45 behavioral variant frontotemporal dementia [bvFTD], 18 progressive nonfluent aphasia [PNFA], 16 semantic dementia [SD]), 22 progressive supranuclear palsy, 50 Alzheimer disease, 6 Parkinson disease, and 17 corticobasal syndrome patients. Correlations between CSF analyte levels were performed with neuropsychological measures and the Clinical Dementia Rating scale sum of boxes (CDRsb). Voxel-based morphometry of structural magnetic resonance images determined the relationship between brain volume and CSF NfL. Results Mean CSF NfL concentrations were higher in bvFTD, SD, and PNFA than other groups. NfL in NC2 was similar to NC. CSF NfL, but not other CSF measures, correlated with CDRsb and neuropsychological measures in FTD, but not in other diagnostic groups. Analyses in 2 independent FTD cohorts and a group of autopsy-verified or biomarker-enriched cases confirmed the larger group analysis. In FTD, gray and white matter volume negatively correlated with CSF NfL concentration, such that individuals with the highest NfL levels exhibited the most atrophy. Interpretation CSF NfL is elevated in symptomatic FTD and correlates with disease severity. This measurement may be a useful surrogate endpoint of disease severity in FTD clinical trials. Longitudinal studies of CSF NfL in FTD are warranted.
Key findings
- Results Mean CSF NfL concentrations were higher in bvFTD, SD, and PNFA than other groups.
Why it matters
In people with frontotemporal degeneration, higher cerebrospinal fluid neurofilament light chain levels tracked with disease severity and worse cognition. This marker reflects disease severity in frontotemporal degeneration and is not a treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 58/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 249 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 17.8 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 10.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 24 other studies in this library |
| Still being cited | 2 / 4 | Cited 29 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Adam L. Boxer: h-index 98 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Los Angeles: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24242746) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
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Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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
Scherling, C. S., Hall, T., Berisha, F., Klepac, K., Karydas, A., Coppola, G., et al. (2014). Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration. Annals of neurology. https://doi.org/10.1002/ana.24052
Vancouver
Scherling CS, Hall T, Berisha F, Klepac K, Karydas A, Coppola G, et al. Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration. Annals of neurology. 2014. doi:10.1002/ana.24052. PMID: 24242746.
BibTeX
@article{scherling2014-24242746,
author = {Scherling, C. S. and Hall, T. and Berisha, F. and Klepac, K. and Karydas, A. and Coppola, G. and Kramer, J. H. and Rabinovici, G. and others},
title = {{Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration}},
journal = {Annals of neurology},
year = {2014},
doi = {10.1002/ana.24052},
pmid = {24242746},
url = {https://doi.org/10.1002/ana.24052}
}
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