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The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: A systematic review and meta‐analysis
Open accessAbstract
Introduction: A systematic review and meta‐analysis was performed regarding the diagnostic performance of neurofilament light chain (NfL) in CSF and blood. Methods: A database search was conducted for NfL biomarker studies in the context of Alzheimer's disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) compared with controls (i.e., cognitively unimpaired, mild cognitive impairment, or disease mimics). Results: In groups with a sufficient number of studies, the performance of NfL in blood and CSF was similar. Compared with disease mimics, we observed that CSF NfL had strong discriminatory power for ALS, modest discriminatory power for FTD, and no discriminatory power for AD. NfL provided the greatest separation between ALS and cognitively unimpaired controls in both the blood and CSF, followed by FTD (CSF and blood), then AD (blood and CSF). Discussion: Comparable performance of CSF and blood NfL in many groups demonstrates the promise of NfL as a noninvasive biomarker of neurodegeneration; however, its utility in clinically meaningful scenarios requires greater scrutiny. Toward clinical implementation, a more comprehensive understanding of NfL concentrations in disease subtypes with overlapping phenotypes and at defined stages of disease, and the development of a harmonization program, are warranted.
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“Similar to what was observed in CSF, serum and plasma NfL are elevated in FTD compared to AD, but with limited utility in discriminating FTD from AD.”
From New developments of biofluid‐based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia (2022) · cites this paper as [89]
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Mead, R. J., Shan, N., Reiser, H. J., Marshall, F., & Shaw, P. J. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00612-2 · Cited by 505
Pathogenesis, diagnostics, and therapeutics for Alzheimer's disease: Breaking the memory barrier
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Frontotemporal lobar degeneration
Grossman, M., Seeley, W. W., Boxer, A. L., Hillis, A. E., Knopman, D. S., Ljubenov, P. A., Miller, B., Piguet, O., Rademakers, R., Whitwell, J. L., et al. (2023) · Nature Reviews Disease Primers · doi:10.1038/s41572-023-00447-0 · Cited by 178
Metadata
- Authors
- Forgrave, L. M., Ma, M., Best, J. R., & DeMarco, M. L.
- Affiliations
- University of British Columbia (CA)
- Providence Health Care (CA)
- Corresponding author
- DeMarco, Mari L.
- Venue
- Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
- Publisher
- Wiley
- Published
- 2019-12
- Volume
- 11
- Issue
- 1
- Pages
- 730-743
- ISSN
- 2352-8729 (ISSN-L)
- PMC
- PMC6939029
- OpenAlex
- W2984229501
- Cited by
- 177
- References
- 87
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 21 · 2023: 41 · 2022: 26 · 2021: 27 · 2020: 22 · 2019: 1
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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
- neurofilament light chain, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, cerebrospinal fluid biomarkers, blood biomarkers, diagnostic accuracy, neurodegeneration, mild cognitive impairment
About these checks
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.
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