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Cited by 28Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Comparison of CSF and plasma NfL and pNfH for Alzheimer's disease diagnosis: a memory clinic study

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Vrillon, Agathe, Ashton, Nicholas J., Karikari, Thomas K., Götze, Karl, Cognat, Emmanuel, Dumurgier, Julien, Lilamand, Matthieu, Zetterberg, Henrik +2 more·2024·Journal of Neurology
DOI 10.1007/s00415-023-12066-6
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Abstract

Abstract Background Plasma neurofilament light chain (NfL) is a promising biomarker of axonal and neuronal damage in central nervous system disorders, displaying potential for the differential diagnosis of neurodegenerative diseases. The heavy chain of the neurofilaments, and specifically the phosphorylated form (pNfH), has demonstrated its value in amyotrophic lateral sclerosis diagnosis but has much less been explored in neurocognitive disorders. Our aim was to compare the positive and differential diagnosis performance of NfL, CSF and plasma pNfH in patients from daily clinical practice in Alzheimer’s disease (AD) and other dementias.Methods In a cross-sectional retrospective study, we compared NfL and pNfH levels in CSF and plasma for AD diagnosis in n = 188 patients from the Center of Cognitive Neurology, Lariboisiere Hospital, Paris, France including AD at the mild cognitive impairment (MCI) stage (AD-MCI, n = 36) and at the dementia stage (n = 64), as well as non-AD MCI (n = 38), non-AD dementia (n = 28) patients and neurological controls (NC) (n = 22). Plasma NfL, plasma and CSF pNfH levels were measured using the Simoa technique and CSF NfL using Elisa.Results NfL and pNfH, in plasma and CSF, were associated with age (rho = 0.259–0.451, P < 0.003). The correlation between CSF and plasma levels was stronger for NfL than pNfH (respectively, rho = 0.77 and rho = 0.52, respectively). Both CSF and plasma NfL and CSF pNfH were associated with CSF p-tau levels in AD patients, but not plasma pNfH. All neurofilament markers were increased in AD-MCI, AD dementia and non-AD dementia compared with NC. CSF NfL, CSF pNfH and plasma NfL showed high performance to discriminate AD at both MCI and dementia stage from control subjects (AUC = 0.82–0.91). Conversely, plasma pNfH displayed overall lower AUCs for discrimination between groups compared with CSF pNfH. Nfs markers showed moderate association with cognition. NfL displayed significant association with mediotemporal lobe atrophy and white matter lesions, in the whole cohort and in the AD subgroup.Conclusion CSF NfL and pNfH as well as plasma NfL displayed equivalent performance in both positive and differential AD diagnosis in a memory clinic setting. In contrast to motoneuron disorders, plasma pNfH did not demonstrate added value as compared with plasma NfL.

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  • Previous studies found plasma NfL correlated relatively strongly with CSF NfL levels (r = 0.64-0.86; sample size 78-188).

    “including some that found plasma NfL correlated relatively strongly with CSF NfL levels (r = 0.64‐0.86; sample size 78‐188), 38 , 40 , 43”

    From A genetic and proteomic comparison of key AD biomarkers across tissues (2024) · cites this paper as [40]

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Authors
Vrillon, A., Ashton, N. J., Karikari, T. K., Götze, K., Cognat, E., Dumurgier, J., Lilamand, M., Zetterberg, H., Blennow, K., & Paquet, C.
Affiliations
  • Inserm (FR)
  • King's College London (GB)
  • University of Pittsburgh (US)
  • Université Paris Cité (FR)
  • University of Wisconsin–Madison (US)
  • Sahlgrenska University Hospital (SE)
Corresponding author
Vrillon, Agathe
ORCID
Venue
Journal of Neurology
Publisher
Springer Science and Business Media LLC
Published
2023-11-11
Volume
271
Issue
3
Pages
1297-1310
ISSN
  • 0012-1037 (ISSN-L)
  • 0340-5354
  • 1432-1459
DOI
10.1007/s00415-023-12066-6
OpenAlex
W4388597408
Cited by
28
References
5
Citations by year
2026: 6 · 2025: 13 · 2024: 9
FWCI
5.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neurology (publishedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
Funders
  • Fondation Ophtalmologique Adolphe de Rothschild
  • Fondation Philippe Chatrier
  • Association Amicale des Anciens Internes des Hopitaux de Paris
  • Fondation Vaincre Alzheimer
  • Demensfonden
  • Gun och Bertil Stohnes Stiftelse
  • Stiftelsen för Gamla Tjänarinnor
  • Wallenberg Centre for Molecular and Translational Medicine
  • Alzheimerfonden (AF-940244)
  • Hjärnfonden (FO2021-0298)
  • BrightFocus Foundation (A2020812F)
  • International Society for Neurochemistry’s Career Development Grant
  • Demensförbundet
  • Parkinsonfonden
  • Aina Wallströms and Mary-Ann Sjöbloms Foundation
  • Agneta Prytz-Folkes och Gösta Folkes Stiftelse (2020-00124)
  • Anna-Lisa och Bror Björnssons Stiftelse
  • H2020 European Research Council (2018-02532)
  • Swedish State Support for Clinical Research (ALFGBG-720931)
  • Alzheimer's Drug Discovery Foundation (201809-2016862)
  • AD Strategic Fund and the Alzheimer’s Association (ADSF-21-831376-C)
  • Olav Thon Stiftelsen
  • Familjen Erling-Perssons Stiftelse
  • HORIZON EUROPE Marie Sklodowska-Curie Actions (860197)
  • UK Dementia Research Institute
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 › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, neurofilament light chain, phosphorylated neurofilament heavy chain, cerebrospinal fluid biomarkers, plasma biomarkers, mild cognitive impairment, dementia diagnosis, differential diagnosis, axonal injury, white matter lesions, memory clinics
MeSH terms
Alzheimer Disease, Cross-Sectional Studies, Humans, Nervous System Diseases, Biomarkers, Motor Neuron Disease, tau Proteins, Neurofilament Proteins, Cognitive Dysfunction

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