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

Landqvist, Maria LU ; Santillo, Alexander LU ; Passant, Ulla LU ; Zetterberg, Henrik; Rosengren, Lars; Nilsson, Christer LU and Englund, Elisabet LU (2013) In BMC Neurology 13.
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),... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Semantic dementia, Neuropathology, Clinical diagnosis
in
BMC Neurology
volume
13
publisher
BioMed Central
external identifiers
  • wos:000319829100001
  • scopus:84878228585
ISSN
1471-2377
DOI
10.1186/1471-2377-13-54
language
English
LU publication?
yes
id
204f92f1-892d-460b-abfd-d138abf7f17c (old id 3927283)
date added to LUP
2013-08-01 07:35:45
date last changed
2019-02-27 03:02:44
@article{204f92f1-892d-460b-abfd-d138abf7f17c,
  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&lt;0.001) and controls (p&lt;0.001). The NFL levels of SD and bvFTD were significantly higher (p&lt;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.},
  articleno    = {54},
  author       = {Landqvist, Maria and Santillo, Alexander and Passant, Ulla and Zetterberg, Henrik and Rosengren, Lars and Nilsson, Christer and Englund, Elisabet},
  issn         = {1471-2377},
  keyword      = {Semantic dementia,Neuropathology,Clinical diagnosis},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {BMC Neurology},
  title        = {Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia},
  url          = {http://dx.doi.org/10.1186/1471-2377-13-54},
  volume       = {13},
  year         = {2013},
}