Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 Oct 21;22(1):953.
doi: 10.1186/s12967-024-05767-7.

CSF and blood levels of Neurofilaments, T-Tau, P-Tau, and Abeta-42 in amyotrophic lateral sclerosis: a systematic review and meta-analysis

Elmira Agah  1   2 , Helia Mojtabavi #  2   3 , Atefeh Behkar #  4 , Arash Heidari #  5   6 , Atra Ajdari #  2 , Zoha Shaka  2 , Seyed Vahid Mousavi  1 , Negar Firoozeh  7 , Abbas Tafakhori  8 , Nima Rezaei  9
Affiliations
Meta-Analysis

CSF and blood levels of Neurofilaments, T-Tau, P-Tau, and Abeta-42 in amyotrophic lateral sclerosis: a systematic review and meta-analysis

Elmira Agah et al. J Transl Med. .

Abstract

Recent literature suggests that markers of neuroaxonal damage, such as neurofilaments and tau protein, might serve as potential biomarkers for ALS. We conducted this systematic review and meta-analysis study to compare cerebrospinal fluid (CSF) and blood levels of total tau (t-tau), phosphorylated tau (p-tau), amyloid beta peptide 42 (Abeta-42), and neurofilaments in ALS patients and controls. A systematic search of Cochrane Library, PubMed, Embase, and ISI Web of Science was conducted on March 18, 2022, and updated on January 26, 2023. Observational studies that compared the concentrations of neurofilament light chain (NfL), neurofilament heavy chain (NFH), t-tau, p-tau, or Abeta-42 in CSF or peripheral blood of ALS patients and controls were included. Data from relevant studies were independently extracted and screened for quality using a standard tool, by at least two authors. Meta-analysis was conducted when a minimum of 3 studies reported the same biomarker within the same biofluid. A total of 100 studies were eligible for at least one meta-analysis. CSF and blood levels of NfL (standardized mean difference (SMD) [95% CI]; CSF: 1.46 [1.25-1.68]; blood: 1.35 [1.09-1.60]) and NFH (CSF: 1.32 [1.13-1.50], blood: 0.90 [0.58-1.22]) were significantly higher in ALS patients compared with controls. The pooled differences between ALS patients and controls were not significant for CSF t-tau, blood t-tau, and CSF Abeta-42, but CSF p-tau was lower in ALS patients (-0.27 [-0.47- -0.07]). Significantly decreased p-tau/t-tau ratios were found in ALS patients compared with controls (-0.84 [-1.16- -0.53]). Heterogeneity was considerable in most of our meta-analyses. CSF and blood neurofilament levels, as well as the CSF p-tau/t-tau ratio, might be potential candidates for improving ALS diagnosis. Further research is warranted to better understand the underlying mechanisms and the clinical implications of these biomarker alterations.

Keywords: ALS; Abeta-42; Alzheimer’s disease biomarkers; Amyotrophic lateral sclerosis; Biomarkers; Meta-analysis; Neurofilaments; Phosphorylated-tau; Systematic review; Total-tau.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flowchart of selected papers. Abeta-42, amyloid beta peptide 42; NFH, neurofilament heavy chain; NfL, neurofilament light chain; PRISMA, preferred reporting items for systematic reviews and meta-analyses; p-tau, phosphorylated tau; t-tau, total tau
Fig. 2
Fig. 2
Meta-analysis of CSF and Blood NfL levels in ALS patients compared with Con (A & E), HCs (B & F), NNCs (C & G), and NCs (D & H). ALS, amyotrophic lateral sclerosis; CI, confidence interval; Con, all non-ALS controls; CSF, cerebrospinal fluid; ECL, electrochemiluminescence; ELISA, enzyme-linked immunoassay; HCs, healthy controls; NCs, neurodegenerative controls; NfL, neurofilament light chain; NNCs, non-neurodegenerative controls; SIMOA, single molecule array; SMD, standardized mean difference
Fig. 3
Fig. 3
Meta-analysis of CSF and Blood NFH levels in ALS patients compared with Con (A & E), HCs (B & F), NNCs (C), and NCs (D & G). ALS, amyotrophic lateral sclerosis; CI, confidence interval; Con, all non-ALS controls; CSF, cerebrospinal fluid; ECL, electrochemiluminescence; ELISA, enzyme-linked immunoassay; HCs, healthy controls; NCs, neurodegenerative controls; NFH, neurofilament heavy chain; NNCs, non-neurodegenerative controls; SIMOA, single molecule array; SMD, standardized mean difference
Fig. 4
Fig. 4
Meta-analysis of CSF Abeta-42 levels in ALS patients compared with Con (A), HCs (B), NNCs (C), and NCs (D). Abeta-42, amyloid beta peptide 42; ALS, amyotrophic lateral sclerosis; CI, confidence interval; Con, all non-ALS controls; CSF, cerebrospinal fluid; ELISA, enzyme-linked immunoassay; HCs, healthy controls; NCs, neurodegenerative controls; NNCs, non-neurodegenerative controls; SMD, standardized mean difference
Fig. 5
Fig. 5
Meta-analysis of CSF and blood t-tau levels in ALS patients compared with Con (A & E), HCs (B), NNCs (C & F), and NCs (D). ALS, amyotrophic lateral sclerosis; CI, confidence interval; CLEIA, chemiluminescence enzyme immunoassay; Con, all non-ALS controls; CSF, cerebrospinal fluid; ELISA, enzyme-linked immunoassay; HCs, healthy controls; NCs, neurodegenerative controls; NNCs, non-neurodegenerative controls; SIMOA, single molecule array; SMD, standardized mean difference; t-tau, total tau
Fig. 6
Fig. 6
Meta-analysis of CSF p-tau levels in ALS patients compared with Con (A), HCs (B), NNCs (C), and NCs (D). ALS, amyotrophic lateral sclerosis; CI, confidence interval; Con, all non-ALS controls; CSF, cerebrospinal fluid; HCs, healthy controls; NCs, neurodegenerative controls; NNCs, non-neurodegenerative controls; p-tau, phosphorylated tau; SMD, standardized mean difference
Fig. 7
Fig. 7
Meta-analysis of CSF p-tau/t-tau ratios in ALS patients compared with Con (A), HCs (B), and NNCs (C). ALS, amyotrophic lateral sclerosis; CI, confidence interval; Con, all non-ALS controls; CSF, cerebrospinal fluid; HCs, healthy controls; NNCs, non-neurodegenerative controls; p-tau, phosphorylated tau; SMD, standardized mean difference; t-tau, total tau
Fig. 8
Fig. 8
The schematic results of this study. Abeta-42, amyloid beta peptide 42; AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; ALSmd, ALS mimic disorders; Con, all non-ALS controls; CSF, cerebrospinal fluid; FTLD, frontotemporal lobar degeneration; HCs, healthy controls; MND, motor neuron disease; NCs, neurodegenerative controls; NFH, neurofilament heavy chain; NfL, neurofilament light chain; NNCs, non-neurodegenerative controls; p-tau, phosphorylated tau; t-tau, total tau
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Longinetti E, Fang F. Epidemiology of amyotrophic lateral sclerosis: an update of recent literature. Curr Opin Neurol. 2019;32(5):771–6. 10.1097/wco.0000000000000730. - PMC - PubMed
    1. Brooks BR, Miller RG, Swash M, Munsat TL. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis and other motor neuron disorders: official publication of the World Federation of Neurology. Res Group Motor Neuron Dis. 2000;1(5):293–9. 10.1080/146608200300079536. - PubMed
    1. Boekestein WA, Kleine BU, Hageman G, Schelhaas HJ, Zwarts MJ. (2010) Sensitivity and specificity of the ‘Awaji’ electrodiagnostic criteria for amyotrophic lateral sclerosis: retrospective comparison of the Awaji and revised El Escorial criteria for ALS. Amyotrophic lateral sclerosis: official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases 11 (6):497–501. 10.3109/17482961003777462 - PubMed
    1. Shefner JM, Al-Chalabi A, Baker MR, Cui LY, de Carvalho M, Eisen A, Grosskreutz J, Hardiman O, Henderson R, Matamala JM, Mitsumoto H, Paulus W, Simon N, Swash M, Talbot K, Turner MR, Ugawa Y, van den Berg LH, Verdugo R, Vucic S, Kaji R, Burke D, Kiernan MC. A proposal for new diagnostic criteria for ALS. Clin Neurophysiology: Official J Int Federation Clin Neurophysiol. 2020;131(8):1975–8. 10.1016/j.clinph.2020.04.005. - PubMed
    1. Goutman SA, Hardiman O, Al-Chalabi A, Chió A, Savelieff MG, Kiernan MC, Feldman EL. Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis. Lancet Neurol. 2022;21(5):480–93. 10.1016/s1474-4422(21)00465-8. - PMC - PubMed

MeSH terms