CoChat
Sign Up
Cited by 36Neuroinflammation and Neurodegeneration MechanismsCerebrospinal fluid and hydrocephalusTraumatic Brain Injury and Neurovascular Disturbances

Distribution of five clinically important neuroglial proteins in the human brain

Open access
Sjölin, Karl, Kultima, Kim, Larsson, Anders, Freyhult, Eva, Zjukovskaja, Christina, Alkass, Kanar, Burman, Joachim·2022·Molecular Brain
DOI 10.1186/s13041-022-00935-6PMC PMC9241296
Open this paper in CoChat — free accountOpen PDF

Abstract

Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), neurofilament light chain (NFL), tau and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are five neuroglial proteins that are used as CSF or blood biomarkers of tissue damage in the nervous system. There is incomplete knowledge of how the concentration of these proteins differs between anatomical regions in the CNS as previous studies have focused on gene expression or non-quantitative protein analyses, limiting the interpretability of these biomarkers. The purpose of this study was to create a map of the tissue content of these proteins in different regions of the CNS. The concentrations of the investigated proteins were determined with ELISA in post mortem tissue homogenates from 17 selected anatomical regions in the CNS from ten deceased donors aged 24 to 50 years. When appropriate, the protein concentrations were adjusted for post-mortem interval. In total, 168 tissue samples were analysed. There was a substantial variation in the concentrations of GFAP, MBP, NFL, tau and UCHL1 between different CNS regions. Highly myelinated areas of the CNS had tenfold higher MBP concentration than cerebral cortex, whereas tau showed an inverse pattern. GFAP, NFL and tau displayed an anteroposterior gradient in cerebral white matter. The cerebellum had low concentrations of all the investigated proteins. In conclusion, the tissue concentrations of GFAP, MBP, NFL, tau and UCHL1 were determined throughout the CNS. This information can be used as a reference when interpreting circulating levels of these biomarkers in relation to the extent and localisation of CNS-damaging processes.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s13041-022-00935-6

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Tau is predominantly expressed in cortical and hippocampal neurons, with expression also in oligodendrocytes and astrocytes.

    “Tau is predominantly expressed in cortical and hippocampal neurons [5–7], although there is also expression in other cell types such as oligodendrocytes and astrocytes [8, 9].”

    From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [5]

    The citation is attached to the claim that tau is expressed in oligodendrocytes and astrocytes. The Results (Distribution of neuroglial proteins; page unavailable) measure tau in anatomical tissue regions, not individual cell types. Searches for oligodendrocytes, astrocytes, and glial expression found no passage addressing that claim. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 28

  1. [1]Khalil M Teunissen CE Otto M Piehl F Sormani MP Gattringer T Neurofilaments as biomarkers in neurological disorders Nat Rev Neurol 2018 14 10 577 589 10.1038/s41582-018-0058-z 30171200 · DOI · Paper page
  2. [2]Petzold A Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease Brain Res 2015 1600 17 31 10.1016/j.brainres.2014.12.027 25543069 · DOI
  3. [3]Graham NSN Zimmerman KA Moro F Heslegrave A Maillard SA Bernini A Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury Sci Transl Med. 2021 13 613 eabg9922 10.1126/scitranslmed.abg9922 34586833 · DOI
  4. [4]Jeans A Esiri M Brain histology Pract Neurol 2008 8 5 303 310 10.1136/jnnp.2008.156893 18796585 · DOI
  5. [5]Sjöstedt E Zhong W Fagerberg L Karlsson M Mitsios N Adori C An atlas of the protein-coding genes in the human, pig, and mouse brain Science 2020 367 6482 eaay5947 10.1126/science.aay5947 32139519 · DOI · Paper page
  6. [6]Kuhle J Barro C Andreasson U Derfuss T Lindberg R Sandelius Å Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa Clin Chem Lab Med 2016 54 10 1655 1661 10.1515/cclm-2015-1195 27071153 · DOI · Paper page
  7. [7]Fountoulakis M Hardmeier R Höger H Lubec G Postmortem changes in the level of brain proteins Exp Neurol 2001 167 1 86 94 10.1006/exnr.2000.7529 11161596 · DOI
  8. [8]García-Sevilla JA Ventayol P Busquets X La Harpe R Walzer C Guimón J Marked decrease of immunolabelled 68 kDa neurofilament (NF-L) proteins in brains of opiate addicts NeuroReport 1997 8 7 1561 1566 10.1097/00001756-199705060-00003 9189892 · DOI
  9. [9]Barker R Wellington D Esiri MM Love S Assessing white matter ischemic damage in dementia patients by measurement of myelin proteins J Cereb Blood Flow Metab 2013 33 7 1050 1057 10.1038/jcbfm.2013.46 23532085 PMC3705431 · DOI
  10. [10]Petzold A Eikelenboom MJ Gveric D Keir G Chapman M Lazeron RHC Markers for different glial cell responses in multiple sclerosis: clinical and pathological correlations Brain 2002 125 7 1462 1473 10.1093/brain/awf165 12076997 · DOI
  11. [11]Petzold A Tozer DJ Schmierer K Axonal damage in the making: neurofilament phosphorylation, proton mobility and magnetisation transfer in multiple sclerosis normal appearing white matter Exp Neurol 2011 232 2 234 239 10.1016/j.expneurol.2011.09.011 21958956 PMC3277890 · DOI
  12. [12]Wang GP Khatoon S Iqbal K Grundke-Iqbal I Brain ubiquitin is markedly elevated in Alzheimer disease Brain Res 1991 566 1–2 146 151 10.1016/0006-8993(91)91692-T 1814531 · DOI
  13. [13]Billington S Salphati L Hop CECA Chu X Evers R Burdette D Interindividual and regional variability in drug transporter abundance at the human blood-brain barrier measured by quantitative targeted proteomics Clin Pharmacol Ther 2019 106 1 228 237 10.1002/cpt.1373 30673124 · DOI
  14. [14]Hawrylycz MJ Lein ES Guillozet-Bongaarts AL Shen EH Ng L Miller JA An anatomically comprehensive atlas of the adult human brain transcriptome Nature 2012 489 7416 391 399 10.1038/nature11405 22996553 PMC4243026 · DOI · Paper page
  15. [15]Vogel C Marcotte EM Insights into the regulation of protein abundance from proteomic and transcriptomic analyses Nat Rev Genet 2012 13 4 227 232 10.1038/nrg3185 22411467 PMC3654667 · DOI · Paper page
  16. [16]Di Meo A Sohaei D Batruch I Alexandrou P Prassas I Diamandis EP Proteomic profiling of the human tissue and biological fluid proteome J Proteome Res 2021 20 1 444 452 10.1021/acs.jproteome.0c00502 33107741 · DOI
  17. [17]Rissin DM Kan CW Campbell TG Howes SC Fournier DR Song L Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations Nat Biotechnol 2010 28 6 595 599 10.1038/nbt.1641 20495550 PMC2919230 · DOI · Paper page
  18. [18]Gisslén M Price RW Andreasson U Norgren N Nilsson S Hagberg L Plasma concentration of the neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: a cross-sectional study EBioMedicine 2016 3 135 140 10.1016/j.ebiom.2015.11.036 26870824 PMC4739412 · DOI · Paper page
  19. [19]Thebault S Booth RA Rush CA MacLean H Freedman MS Serum neurofilament light chain measurement in MS: hurdles to clinical translation Front Neurosci 2021 15 334 10.3389/fnins.2021.654942 PMC8027110 33841093 · DOI
  20. [20]Bittner S Oh J Havrdová EK Tintoré M Zipp F The potential of serum neurofilament as biomarker for multiple sclerosis Brain 2021 144 10 2954 2963 10.1093/brain/awab241 34180982 PMC8634125 · DOI
  21. [21]Tiedt S Duering M Barro C Kaya AG Boeck J Bode FJ Serum neurofilament light Neurology 2018 91 14 e1338 e1347 10.1212/WNL.0000000000006282 30217937 · DOI
  22. [22]O’Connell GC Alder ML Smothers CG Still CH Webel AR Moore SM Diagnosis of ischemic stroke using circulating levels of brain-specific proteins measured via high-sensitivity digital ELISA Brain Res 2020 1739 146861 10.1016/j.brainres.2020.146861 32353434 PMC7409378 · DOI
  23. [23]Jauch EC Lindsell C Broderick J Fagan SC Tilley BC Levine SR Association of serial biochemical markers with acute ischemic stroke: The National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study Stroke 2006 37 10 2508 2513 10.1161/01.STR.0000242290.01174.9e 16960091 · DOI
  24. [24]Pujol-Calderón F Zetterberg H Portelius E Löwhagen Hendén P Rentzos A Karlsson J-E Prediction of outcome after endovascular embolectomy in anterior circulation stroke using biomarkers Transl Stroke Res 2022 13 1 65 76 10.1007/s12975-021-00905-5 33723754 PMC8766380 · DOI
  25. [26]Siller N Kuhle J Muthuraman M Barro C Uphaus T Groppa S Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis Mult Scler J 2019 25 5 678 686 10.1177/1352458518765666 29542376 · DOI
  26. [27]Aktas O Smith MA Rees WA Bennett JL She D Katz E Serum glial fibrillary acidic protein: a neuromyelitis optica spectrum disorder biomarker Ann Neurol 2021 89 5 895 910 10.1002/ana.26067 33724534 PMC8252046 · DOI
  27. [28]Olczak M Kwiatkowska M Niderla-Bielińska J Chutorański D Tarka S Wierzba-Bobrowicz T Brain-originated peptides as possible biochemical markers of traumatic brain injury in cerebrospinal fluid post-mortem examination Folia Neuropathol 2018 56 2 97 103 10.5114/fn.2018.76613 30509029 · DOI
  28. [29]Olczak M Niderla-Bielińska J Kwiatkowska M Samojłowicz D Tarka S Wierzba-Bobrowicz T Tau protein (MAPT) as a possible biochemical marker of traumatic brain injury in postmortem examination Forensic Sci Int 2017 280 1 7 10.1016/j.forsciint.2017.09.008 28942078 · DOI

Cited by

Sorted by citations

Authors
Sjölin, K., Kultima, K., Larsson, A., Freyhult, E., Zjukovskaja, C., Alkass, K., & Burman, J.
Affiliations
  • Uppsala University Hospital (SE)
  • Uppsala University (SE)
  • Karolinska Institutet (SE)
Corresponding author
Sjölin, Karl
ORCID
Venue
Molecular Brain
Publisher
Springer Science and Business Media LLC
Published
2022-06-29
Volume
15
Issue
1
Pages
52-52
ISSN
1756-6606 (ISSN-L)
DOI
10.1186/s13041-022-00935-6
PMC
PMC9241296
OpenAlex
W4283689152
Cited by
36
References
1
Citations by year
2026: 5 · 2025: 9 · 2024: 10 · 2023: 11 · 2022: 1
FWCI
2.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Brain (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Bissen Brainwalk
  • Swedish state support for research
  • Uppsala University
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
glial fibrillary acidic protein, myelin basic protein, neurofilament light chain, tau protein, UCHL1, human brain, postmortem interval, cerebellum, white matter, reference values
MeSH terms
Autopsy, Brain, Humans, Biomarkers, Ubiquitin Thiolesterase, White Matter

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.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review