GFAP degradation in TBI: linking novel modified products to astrocyte pathology and patient outcome.
Overview
- Semel Institute for Neuroscience and Human Behavior, Intellectual and Developmental Disability Center (IDDRC), Brain Injury Research Center (BIRC), David Geffen School of Medicine, UCLA, 635 Charles E. Young Drive South, NRB315, Los Angeles, CA 90095 USA
- Department of Chemistry and Biochemistry, Molecular Biology Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA USA
- Molecular Instrumentation Center (MIC), Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA USA
- Department of Anesthesiology, Neurosurgery and Neuroscience, University of Florida, Gainesville, FL 32610-0254 USA
- Department of Radiological Sciences, Geffen School of Medicine, UCLA, Los Angeles, CA USA
- Department of Computational Medicine, Statistics Core of the Department of Medicine, School of Public Health, UCLA, Los Angeles, CA USA
- BRAINBox Solutions, Inc., Richmond, VA 23219 USA
- Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL 32610 USA
- EnCor Biotechnology Inc., Gainesville, FL 32608 USA
- Department Neurology and Neurosurgery, BIRC, David Geffen School of Medicine, Ronald Reagan Medical Center, UCLA, Los Angeles, CA USA
Abstract
Glial fibrillary acidic protein (GFAP) is a significant clinical biomarker of traumatic brain injury (TBI), yet understanding the nature, timing, and impact of its degraded and modified products would inform clinical utility. We report novel GFAP breakdown products (BDPs) and post-translational modifications (PTMs) that are unique to TBI including fragment- and patient-specific citrullination signatures that destabilize GFAP filaments. GFAP and its fragments were sequenced by mass spectrometry (MS) from severe TBI patients’ cerebrospinal fluid (CSF) and sera, identifying two distinct TBI-specific jointly generated product sets within the rod-domain covering coil1 (20–26 kDa) and coil2 (15–19 kDa). Their endings differed from GFAP fragments described in Alzheimer’s and Alexander disease. Label-free quantification showed biofluid co-product abundance differences with coil1-BDPs enriched over coil2-BDPs. Coil imbalance was independently confirmed by immunoblot densitometry in twenty-three TBI patients. Measurements over ten days showed injury day peaks of full-length and end-clipped GFAP fragments, while proteolytic 37/
Supplementary Information: The online version contains supplementary material available at 10.1186/
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper links to its data, not to its authors' code: see the Data section.
The paper's code and data availability statement is in the Data section.
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Data
Datasets cited
- uniprot.org/
uniprotkb/ , at UniProt; found in the text, “Immunoprecipitation and mass spectrometry…”p14136
Data availability
Dataset for longitudinal CSF quantification of GFAP and its fragments is available in Open Data Commons TBI: https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 8 keywords, 13 MeSH terms, 7 funders, 108 references, 1 RRID.
Cite
This paper
Wanner, I.-B., Halford, J., Lopez, J., Shen, S., Chen, Y., Zhao, H., Salas, C., Loo, R. O., Robicsek, S., Ellingson, B. M., Gornbein, J., Van Meter, T. E., Shaw, G., Loo, J. A., & Vespa, P. M. (2026). GFAP degradation in TBI: linking novel modified products to astrocyte pathology and patient outcome. Acta neuropathologica communications, 14(1), 101. https://
BibTeX
@article{wanner2026gfap,
author = {Wanner, Ina-Beate and Halford, Julia and Lopez, Jonathan and Shen, Sean and Chen, Yu and Zhao, Hayden and Salas, Carolina and Loo, Rachel Ogorzalek and Robicsek, Steven and Ellingson, Benjamin M and Gornbein, Jeffrey and Van Meter, Timothy E and Shaw, Gerry and Loo, Joseph A and Vespa, Paul M},
title = {{GFAP degradation in TBI: linking novel modified products to astrocyte pathology and patient outcome}},
journal = {Acta neuropathologica communications},
year = {2026},
month = apr,
volume = {14},
number = {1},
pages = {101},
publisher = {BMC},
issn = {2051-5960},
doi = {10.1186/
url = {https://
pmid = {42032706},
pmcid = {PMC13107622}
}
RIS
TY - JOUR
AU - Wanner, Ina-Beate
AU - Halford, Julia
AU - Lopez, Jonathan
AU - Shen, Sean
AU - Chen, Yu
AU - Zhao, Hayden
AU - Salas, Carolina
AU - Loo, Rachel Ogorzalek
AU - Robicsek, Steven
AU - Ellingson, Benjamin M
AU - Gornbein, Jeffrey
AU - Van Meter, Timothy E
AU - Shaw, Gerry
AU - Loo, Joseph A
AU - Vespa, Paul M
TI - GFAP degradation in TBI: linking novel modified products to astrocyte pathology and patient outcome
T2 - Acta neuropathologica communications
J2 - Acta Neuropathol Commun
PY - 2026
DA - 2026/
VL - 14
IS - 1
SP - 101
SN - 2051-5960
PB - BMC
DO - 10.1186/
UR - https://
LA - en
ER -
CSL-JSON
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