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Cited by 179Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis Research

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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

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Forgrave, Lauren M., Ma, Matthew, Best, John R., DeMarco, Mari L.·2019·Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
DOI 10.1016/j.dadm.2019.08.009PMC PMC6939029
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Abstract

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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Crossref · 10.1016/j.dadm.2019.08.009

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Fig. 1 Retrieval process of peer-reviewed studies that included NfL quantitation in CSF, plasma, and serum from individuals with AD, ALS, FTD, and controls. Abbreviations: AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; FTD, frontotemporal dementia; NfL, neurofilament light chain.
Fig. 1 Retrieval process of peer-reviewed studies that included NfL quantitation in CSF, plasma, and serum from individuals with AD, ALS, FTD, and controls. Abbreviations: AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; FTD, frontotemporal dementia; NfL, neurofilament light chain.CC BY-NC-ND · PubMed Central
Fig. 2 Comparison of the average ratio of NfL concentration in AD to (A) cognitively unimpaired (CU) controls in CSF, (B) MCI controls in CSF, (C) disease mimic (DM) controls in CSF, (D) cognitively unimpaired controls in blood, and (E) MCI controls in blood. Abbreviations: AD, Alzheimer's disease; NfL, neurofilament light chain; MCI, mild cognitive impairment.
Fig. 2 Comparison of the average ratio of NfL concentration in AD to (A) cognitively unimpaired (CU) controls in CSF, (B) MCI controls in CSF, (C) disease mimic (DM) controls in CSF, (D) cognitively unimpaired controls in blood, and (E) MCI controls in blood. Abbreviations: AD, Alzheimer's disease; NfL, neurofilament light chain; MCI, mild cognitive impairment.CC BY-NC-ND · PubMed Central
Fig. 3 Comparison of average ratio of NfL concentration in FTD to (A) cognitively unimpaired controls in CSF, (B) MCI controls in CSF, (C) disease mimic controls in CSF (D) cognitively unimpaired controls in blood, and (E) MCI controls in blood. Abbreviations: FTD, frontotemporal dementia; NfL, neurofilament light chain; MCI, mild cognitive impairment.
Fig. 3 Comparison of average ratio of NfL concentration in FTD to (A) cognitively unimpaired controls in CSF, (B) MCI controls in CSF, (C) disease mimic controls in CSF (D) cognitively unimpaired controls in blood, and (E) MCI controls in blood. Abbreviations: FTD, frontotemporal dementia; NfL, neurofilament light chain; MCI, mild cognitive impairment.CC BY-NC-ND · PubMed Central
Fig. 4 Comparison of average ratio of NfL concentration in ALS to (A) cognitively unimpaired controls in CSF, (B) disease mimic controls in CSF, (C) cognitively unimpaired controls in blood, and (D) disease mimic controls in blood. Abbreviations: ALS, amyotrophic lateral sclerosis; NfL, neurofilament light chain; MCI, mild cognitive impairment.
Fig. 4 Comparison of average ratio of NfL concentration in ALS to (A) cognitively unimpaired controls in CSF, (B) disease mimic controls in CSF, (C) cognitively unimpaired controls in blood, and (D) disease mimic controls in blood. Abbreviations: ALS, amyotrophic lateral sclerosis; NfL, neurofilament light chain; MCI, mild cognitive impairment.CC BY-NC-ND · PubMed Central
Fig. 5 Summary of the diagnostic performance of NfL concentration in CSF or blood in AD, FTD, and ALS compared to control groups (i.e., cognitively unimpaired, MCI and disease mimics) displayed as average ROM statistic and 95% CI, with the number of studies annotated. Abbreviations: AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; FTD, frontotemporal dementia; NfL, neurofilament light chain: MCI, mild cognitive impairment; ROM, ratio of means.
Fig. 5 Summary of the diagnostic performance of NfL concentration in CSF or blood in AD, FTD, and ALS compared to control groups (i.e., cognitively unimpaired, MCI and disease mimics) displayed as average ROM statistic and 95% CI, with the number of studies annotated. Abbreviations: AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; FTD, frontotemporal dementia; NfL, neurofilament light chain: MCI, mild cognitive impairment; ROM, ratio of means.CC BY-NC-ND · PubMed Central

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  1. Schwarzer G., 2007, meta: an R package for meta‐analysis, R News, 7, 40

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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.
ORCID
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)
DOI
10.1016/j.dadm.2019.08.009
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
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

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