Cerebrospinal fluid apolipoprotein E concentration decreases after traumatic brain injury
Abstract
The APOE epsilon4 allele has been associated with unfavorable outcome after several types of acute brain injury, yet the biological mechanisms underlying this observation are poorly understood. Postmortem and experimental brain injury studies suggest the presence of increased amounts of apolipoprotein E (apoE) within the neuropil after acute brain injury. We assayed the concentration of apolipoprotein E in the cerebrospinal fluid (CSF) of non-injured controls and patients with traumatic brain injury (TBI) to determine whether differences exist, and if these differences correlate with injury severity and clinical outcome. CSF apoE and S100B, a marker of injury severity, were measured by enzyme linked immunosorbant assay. CSF was sampled from 27 traumatic brain injury patients (mean age 32, median 25, range 16-65 years) within 3 days of injury, and 28 controls (mean age 40, median 37, range 19-73 years). The TBI patients all had a Glasgow Coma Score (GCS) of less than eight (i.e., severe head injury). Clinical outcome was determined using the Glasgow Outcome Score (GOS). The average concentration of apoE in the CSF of controls was 12.4 mg/L (95% CI: 10.5-14.3 mg/L) and in TBI patients was 3.7 mg/L (95% CI: 2.1-4.1 mg/L; Mann-Whitney: p < 0.0001). In contrast, the concentration of S100B in the CSF of TBI patients was significantly higher than that of controls (Mann-Whitney: p < 0.0001). We speculate that apoE is retained within the parenchyma of the central nervous system in res…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
The concentration 0.375 M is similar to the reported concentration of apoE in human cerebrospinal fluid (0.365-0.395 M).
“More importantly, toxicity (28% decrease in cell viability) was evident even when lipidated apoE4[L28P] was used at the lower concentration of 0.375 M, which is similar to the reported concentration of apoE in human cerebrospinal fluid (0.365-0.395M) (47,48).”
From Molecular Basis for Increased Risk for Late-onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4 (2014) · cites this paper as [47]
Cites
Lack of apolipoprotein E dramatically reduces amyloid β-peptide deposition
Bales, K. R., Verina, T., Dodel, R. C., Du, Y., Altstiel, L., Bender, M., Hyslop, P., Johnstone, E. M., Little, S. P., Cummins, D. J., et al. (1997) · Nature Genetics · doi:10.1038/ng1197-263 · Cited by 830 · see citing works
Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation.
Linton, M. F., Gish, R., Hubl, S. T., Bütler, E., Esquivel, C., Bry, W. I., Boyles, J. K., Wardell, M. R., & Young, S. G. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115288 · Cited by 367 · see citing works
White, F., Nicoll, J. A. R., Roses, A. D., & Horsburgh, K. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0401 · Cited by 128 · see citing works
Self-citationApolipoprotein E Polymorphism: Survival and Neurological Outcome After Cardiopulmonary Resuscitation
Schiefermeier, M., Kollegger, H., Madl, C., Schwarz, C., Holzer, M., Kofler, J., & Sterz, F. (2000) · Stroke · doi:10.1161/01.str.31.9.2068 · Cited by 72 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
An apolipoprotein E4 fragment can promote intracellular accumulation of amyloid peptide beta 42
Dafnis, I., Stratikos, E., Tzinia, A., Tsilibary, E. C., Zannis, V. I., & Chroni, A. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06756.x · Cited by 41 · see citing works
Argyri, L., Dafnis, I., Theodossiou, T. A., Gantz, D., Stratikos, E., & Chroni, A. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.538124 · Cited by 30 · see citing works
Georgiadou, D., & Chroni, A. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.149644 · Cited by 2 · see citing works
- Authors
- Kay, A. D., Petzold, A., Kerr, M., Keir, G., Thompson, E. J., & Nicoll, J. A. R.
- Affiliations
- Southern General Hospital (GB)
- University of London (GB)
- University of Pittsburgh (US)
- Southampton General Hospital (GB)
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2003-03
- Volume
- 20
- Issue
- 3
- Pages
- 243-250
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- OpenAlex
- W1527305439
- Cited by
- 33
- References
- 4
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurotrauma (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- University of Pittsburgh
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Keywords
- apolipoprotein E, cerebrospinal fluid, traumatic brain injury, APOE ε4, S100B, injury severity, clinical outcomes, neuroprotection, biomarkers, severe traumatic brain injury
- MeSH terms
- Adolescent, Adult, Aged, Albumins, Apolipoproteins E, Brain Injuries, Cerebrospinal Fluid Proteins, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Nerve Growth Factors, S100 Proteins, Prospective Studies, Cohort Studies, Glasgow Coma Scale, Glasgow Outcome Scale, S100 Calcium Binding Protein beta Subunit
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