Serial neoGFAP outperforms total GFAP for monitoring and 6-month outcome discrimination after moderate to severe traumatic brain injury: an exploratory single-site cohort study
- 1Gryphon Bio, Inc., South San Francisco, CA, USA; Owl Therapeutics, LLC, Cambridge, MA, USA
Abstract
BackgroundSerial glial fibrillary acidic protein (GFAP) trajectories have become an important framework for contextualizing evolving secondary-injury pathophysiology after moderate-to-severe traumatic brain injury (msTBI). However, total GFAP pools release and clearance signals that may be less useful for longitudinal bedside decisions than a proteoform-resolved assay. We compared total GFAP with neoGFAP, defined here as calpain-generated GFAP proteoforms intended to index active astroglial proteolysis during the subacute phase.
MethodsWe analyzed 651 serial serum samples from 95 msTBI patients from a previously described single-site cohort. Total GFAP and neoGFAP were measured on the same MSD platform from 6 to 240 hours after injury. Early (6-72 h) and late (96-240 h) windows, data-derived tertiles, and serial trajectory summaries were calculated directly from serial samples. Models were benchmarked against age plus admission post-resuscitation Glasgow Coma Scale (GCS) and the admission IMPACT extended risk score using five-fold stratified cross-validation. Outcomes were unfavorable outcome (GOSE 1-4), less-than-good recovery (GOSE 1-6), Disability Rating Scale (DRS) [≥]15, mortality, and neuroimaging worsening at 6 months.
ResultsThe cohort contributed 95 serial biomarker profiles, with 90 participants evaluable for 6-month GOSE and 89 for DRS. Unfavorable outcome occurred in 57/90 (63.3%), and less-than-good recovery in 79/90 (87.8%). For unfavorable outcome, IMPACT plus early neoGFAP reached AUROC 0.85 versus 0.84 for IMPACT plus early total GFAP and 0.81 for IMPACT alone. For less-than-good recovery, IMPACT plus late neoGFAP achieved AUROC 0.90 versus 0.84 for late total GFAP and 0.82 for IMPACT alone. Secondary analyses for DRS, mortality, and neuroimaging worsening showed smaller differences.
ConclusionsIn this retrospective analysis, neoGFAP provided clearer incremental value than total GFAP for recovery-oriented monitoring, especially when late-window reassessment of patients who remained at risk for less-than-good recovery was required. Results support prospective testing of neoGFAP as a pathophysiology-informed adjunct to serial bedside decision making, repeat-assessment thresholds, and recovery stratification.
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BibTeX
@misc{wang2026serial,
title = {{Serial neoGFAP outperforms total GFAP for monitoring and 6-month outcome discrimination after moderate to severe traumatic brain injury: an exploratory single-site cohort study}},
author = {K. K. Wang and G. Cai and K. Boukholda and F. Kobeissy and E. Elbayoumi and D. Jackson and K. Tehas and K. Radeker and A. DeLizza and C. Popper and S. Tsetsou and C. Robertson and W. E. Haskins},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.26361862},
url = {https://www.medrxiv.org/content/10.64898/2026.09.01.26361862v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Serial neoGFAP outperforms total GFAP for monitoring and 6-month outcome discrimination after moderate to severe traumatic brain injury: an exploratory single-site cohort study
AU - K. K. Wang
AU - G. Cai
AU - K. Boukholda
AU - F. Kobeissy
AU - E. Elbayoumi
AU - D. Jackson
AU - K. Tehas
AU - K. Radeker
AU - A. DeLizza
AU - C. Popper
AU - S. Tsetsou
AU - C. Robertson
AU - W. E. Haskins
PY - 2026
DA - 2026/09/01
PB - medRxiv
DO - 10.64898/2026.09.01.26361862
UR - https://www.medrxiv.org/content/10.64898/2026.09.01.26361862v1
AB - BackgroundSerial glial fibrillary acidic protein (GFAP) trajectories have become an important framework for contextualizing evolving secondary-injury pathophysiology after moderate-to-severe traumatic brain injury (msTBI). However, total GFAP pools release and clearance signals that may be less useful for longitudinal bedside decisions than a proteoform-resolved assay. We compared total GFAP with neoGFAP, defined here as calpain-generated GFAP proteoforms intended to index active astroglial proteolysis during the subacute phase. MethodsWe analyzed 651 serial serum samples from 95 msTBI patients from a previously described single-site cohort. Total GFAP and neoGFAP were measured on the same MSD platform from 6 to 240 hours after injury. Early (6-72 h) and late (96-240 h) windows, data-derived tertiles, and serial trajectory summaries were calculated directly from serial samples. Models were benchmarked against age plus admission post-resuscitation Glasgow Coma Scale (GCS) and the admission IMPACT extended risk score using five-fold stratified cross-validation. Outcomes were unfavorable outcome (GOSE 1-4), less-than-good recovery (GOSE 1-6), Disability Rating Scale (DRS) [≥]15, mortality, and neuroimaging worsening at 6 months. ResultsThe cohort contributed 95 serial biomarker profiles, with 90 participants evaluable for 6-month GOSE and 89 for DRS. Unfavorable outcome occurred in 57/90 (63.3%), and less-than-good recovery in 79/90 (87.8%). For unfavorable outcome, IMPACT plus early neoGFAP reached AUROC 0.85 versus 0.84 for IMPACT plus early total GFAP and 0.81 for IMPACT alone. For less-than-good recovery, IMPACT plus late neoGFAP achieved AUROC 0.90 versus 0.84 for late total GFAP and 0.82 for IMPACT alone. Secondary analyses for DRS, mortality, and neuroimaging worsening showed smaller differences. ConclusionsIn this retrospective analysis, neoGFAP provided clearer incremental value than total GFAP for recovery-oriented monitoring, especially when late-window reassessment of patients who remained at risk for less-than-good recovery was required. Results support prospective testing of neoGFAP as a pathophysiology-informed adjunct to serial bedside decision making, repeat-assessment thresholds, and recovery stratification.
ER -