Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration
Open accessAbstract
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‐β 1–42 (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. ANN NEUROL 2014;75:116–126
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Increased CSF NfL, in both genetic and sporadic subtypes, has been associated with various progression measures, including CDR, cognition, behavioral symptoms, frontotemporal grey matter atrophy, white matter tract pathophysiology, GABA-ergic deficit, and survival rates.
“Increased CSF NfL, in both genetic and sporadic subtypes, has been associated with various progression measures, including CDR, cognition (executive functioning; neuropsychiatry unit cognitive assessment tool), behavioral symptoms (FBI), frontotemporal GM atrophy, WM tract pathophysiology, GABA-ergic deficit, and survival rates”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Scherling et al., 2014
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- Authors
- Scherling, C. S., Hall, T., Berisha, F., Klepac, K., Karydas, A., Coppola, G., Kramer, J. H., Rabinovici, G., Ahlijanian, M., Miller, B. L., Seeley, W., Grinberg, L. T., Rosen, H., Meredith, J., & Boxer, A. L.
- Affiliations
- University of California, San Francisco (US)
- Bristol-Myers Squibb (United States) (US)
- University of California, Los Angeles (US)
- Corresponding author
- Boxer, Adam L.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2014-01
- Volume
- 75
- Issue
- 1
- Pages
- 116-126
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC4020786
- OpenAlex
- W2134323711
- Cited by
- 249
- References
- 33
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 19 · 2023: 13 · 2022: 16 · 2021: 24 · 2020: 27 · 2019: 36 · 2018: 29 · 2017: 24 · 2016: 22 · 2015: 18 · 2014: 11
- FWCI
- 12.09
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Annals of Neurology (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (R01AG038791, R01AG032306)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- frontotemporal lobar degeneration, behavioral variant frontotemporal dementia, progressive nonfluent aphasia, semantic dementia, disease severity markers, amyloid-beta 42, phosphorylated tau, brain atrophy, gray and white matter volume, Clinical Dementia Rating
- MeSH terms
- Adult, Aged, Female, Humans, Male, Middle Aged, Severity of Illness Index, Cohort Studies, Biomarkers, Neurofilament Proteins, Frontotemporal Lobar Degeneration
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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.
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