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Cited by 127Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis Research

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Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia

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Landqvist Waldö, Maria, Frizell Santillo, Alexander, Passant, Ulla, Zetterberg, Henrik, Rosengren, Lars, Nilsson, Christer, Englund, Elisabet·2013·BMC Neurology
DOI 10.1186/1471-2377-13-54PMC PMC3671150
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Abstract

BACKGROUND: Frontotemporal dementia (FTD) is recognised as a clinically and morphologically heterogeneous group of interrelated neurodegenerative conditions. One of the subtypes within this disease spectrum is the behavioural variant FTD (bvFTD). This is known to be a varied disorder with a mixture of tau-positive and tau-negative underlying pathologies. The other subtypes include semantic dementia (SD), which generally exhibits tau-negative pathology, and progressive non-fluent aphasia (PNFA), which is usually tau-positive. As the clinical presentation of these subtypes may overlap, a specific diagnosis can be difficult to attain and today no specific biomarker can predict the underlying pathology. Neurofilament light chain protein (NFL), a cytoskeletal constituent of intermediate filaments, is thought to reflect neuronal and axonal death when appearing in the cerebrospinal fluid (CSF). NFL has been shown to be elevated in CSF in patients with FTD compared with AD and controls. Our hypothesis was that the levels of NFL also differ between the subtypes of FTD and may indicate the underlying pathological subtype. METHODS: We retrospectively analysed data from previous CSF analyses in 34 FTD cases (23 bvFTD, seven SD, four PNFA), 20 AD cases, and 26 healthy controls. A separate group of 10 neuropathologically verified and subtyped FTD cases (seven tau-negative, three tau-positive) were also analysed. RESULT: NFL levels were significantly higher in FTD compared with both AD (p<0.001) and controls (p<0.001). The NFL levels of SD and bvFTD were significantly higher (p<0.001) compared with AD. The biomarker profiles of PNFA and AD were similar. In the neuropathologically verified FTD cases, NFL was higher in the tau-negative than in the tau-positive cases (exact p=0.017). CONCLUSIONS: The marked NFL elevation in some but not all FTD cases is likely to reflect the different underlying pathologies. The highest NFL values found in the SD group as well as in the neuropathologically verified tau-negative cases may be of subtype diagnostic value, if corroborated in larger patient cohorts. In bvFTD, a mixture of tau-positive and tau-negative underlying pathologies could possibly explain the intermediate NFL values.

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Figure 1 Boxplot with individual values of NFL in each clinical subtype. The number of subjects in each subtype: bvFTD n=23, SD n=7, PNFA n=4, AD n=20, healthy controls n=26. The detection limit of NFL was 250 ng/l.
Figure 1 Boxplot with individual values of NFL in each clinical subtype. The number of subjects in each subtype: bvFTD n=23, SD n=7, PNFA n=4, AD n=20, healthy controls n=26. The detection limit of NFL was 250 ng/l.CC BY · PubMed Central
Figure 2 Scatter of NFL values in each neuropathological subtype. The number of subjects in each subtype: tau-positive n=3, tau-negative n=7. The detection limit of NFL was 250 ng/l.
Figure 2 Scatter of NFL values in each neuropathological subtype. The number of subjects in each subtype: tau-positive n=3, tau-negative n=7. The detection limit of NFL was 250 ng/l.CC BY · PubMed Central

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Metadata

Authors
Landqvist Waldö, M., Frizell Santillo, A., Passant, U., Zetterberg, H., Rosengren, L., Nilsson, C., & Englund, E.
Affiliations
  • Skåne University Hospital (SE)
  • National Hospital for Neurology and Neurosurgery (GB)
  • University of Gothenburg (SE)
  • Lund University (SE)
ORCID
Venue
BMC Neurology
Publisher
Springer Science and Business Media LLC
Published
2013-05-29
Volume
13
Issue
1
Pages
54-54
ISSN
1471-2377 (ISSN-L)
DOI
10.1186/1471-2377-13-54
PMC
PMC3671150
OpenAlex
W2141909536
Cited by
127
References
35
Citations by year
2025: 8 · 2024: 1 · 2023: 3 · 2022: 10 · 2021: 7 · 2020: 9 · 2019: 13 · 2018: 22 · 2017: 18 · 2016: 10 · 2015: 12 · 2014: 10 · 2013: 3
FWCI
7.14
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Neurology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Gothenburg University Publications Electronic Archive (Gothenburg University) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion, other-oa)
Funders
Region Skåne
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
frontotemporal dementia, neurofilament light chain, cerebrospinal fluid biomarkers, behavioral variant frontotemporal dementia, semantic dementia, progressive nonfluent aphasia, tau pathology, Alzheimer's disease, neuronal cell death
MeSH terms
Adult, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Male, Middle Aged, Neurologic Examination, Peptide Fragments, Retrospective Studies, Spinal Puncture, Case-Control Studies, Amyloid beta-Peptides, tau Proteins, Neurofilament Proteins, Statistics, Nonparametric, Frontotemporal Dementia

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