CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival
Abstract
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.
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High CSF NfL levels are associated with more severe cognitive impairment and shorter survival time in patients with FTD.
“Neurofilament light chain was chosen because in 2014 several groups reported that high CSF NfL levels were associated with more severe cognitive impairment and shorter survival time in patients with FTD.32,33”
From Association of Cognitive and Behavioral Features Between Adults With Tuberous Sclerosis and Frontotemporal Dementia (2020) · cites this paper as [33]
Increased levels of NfL in CSF and serum, indicating axonal loss, correlated with increased cognitive impairment, with a stronger correlation in serum than in CSF.
“Increased levels of NfL in CSF and serum, indicating axonal loss, correlated with increased cognitive impairment, as has been shown previously [73, 74], with a stronger correlation in serum than in CSF.”
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“Overactivity 6/16 (38) 5/15 (33) 1/16 (6)”
- Authors
- Skillbäck, T., Farahmand, B., Bartlett, J. W., Rosén, C., Mattsson, N., Nägga, K., Kilander, L., Religa, D., Wimo, A., Winblad, B., Rosengren, L., Schott, J. M., Blennow, K., Eriksdotter, M., & Zetterberg, H.
- Affiliations
- Uppsala University (SE)
- ORCID
- Venue
- Neurology
- Published
- 2014-11-18
- Volume
- 83
- Issue
- 21
- Pages
- 1945-1953
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2056196309
- Cited by
- 263
- References
- 36
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 19 · 2023: 13 · 2022: 13 · 2021: 36 · 2020: 39 · 2019: 32 · 2018: 37 · 2017: 24 · 2016: 20 · 2015: 10 · 2014: 1
- FWCI
- 13.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- neurodegeneration biomarkers, dementia, vascular dementia, Alzheimer's disease, frontotemporal dementia, disease severity, survival prediction, early-onset Alzheimer's disease
- MeSH terms
- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Registries, Severity of Illness Index, Biomarkers, Survival Rate, Neurofilament Proteins, Neurodegenerative Diseases
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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