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. 2025 Jan;32(1):e16581.
doi: 10.1111/ene.16581.

Prognostic serum biomarkers of synaptic, neuronal and glial injury in patients with acute ischemic stroke of the anterior circulation

Lorenzo Barba  1 , Christoph Vollmuth  2 , Steffen Halbgebauer  3   4 , Kathrin Ungethüm  5   6 , Christian Hametner  2 , Fabian Essig  2 , Alexander M Kollikowski  7 , Mirko Pham  7 , Michael K Schuhmann  2 , Peter U Heuschmann  5   6   8 , Patrick Oeckl  3   4 , Petra Steinacker  1 , Michele Romoli  9 , Lucio D'Anna  10   11 , Samir Abu-Rumeileh  1 , Karl Georg Haeusler  3 , Guido Stoll  12 , Hermann Neugebauer  2 , Markus Otto  1
Affiliations

Prognostic serum biomarkers of synaptic, neuronal and glial injury in patients with acute ischemic stroke of the anterior circulation

Lorenzo Barba et al. Eur J Neurol. 2025 Jan.

Abstract

Background: We aimed to investigate the prognostic role of β-synuclein in comparison to that of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) for predicting functional outcome after acute ischemic stroke (AIS).

Methods: We measured serum concentrations of β-synuclein, NfL and GFAP 24 h after hospital admission in 213 consecutive patients with moderate-to-severe AIS. We investigated the association between serum biomarkers and radiological/clinical characteristics, 3-months mortality and functional outcome on the modified Rankin Scale (mRS).

Results: In 213 patients with AIS [mean age: 76.1 (±12.5) years, 53.1% males, median NIHSS score on admission: 13 (IQR: 9-17)], higher levels of β-synuclein, NfL and GFAP were associated with higher NIHSS scores and with lower Alberta Stroke Program CT Score (ASPECTS) points on admission. Serum β-synuclein levels was significantly correlated with NfL (rho = 0.715, p < 0.001) and GFAP concentrations (rho = 0.684, p < 0.001). The inclusion of serum β-synuclein significantly improved the accuracy of prediction models without biomarkers for overall mortality (AUC: 0.836 vs. 0.752, p < 0.001) and mRS 3-6 vs. 0-2 (AUC: 0.812 vs. 0.624, p < 0.001). Combination models with NfL and/or GFAP showed a similar accuracy.

Conclusions: Serum β-synuclein may be used to assess synaptic damage/dysfunction and to predict 3-months clinical outcomes in patients with AIS.

Keywords: GFAP; NfL; beta‐synuclein; biomarkers; stroke.

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Conflict of interest statement

MO gave scientific advice for Fujirebio, Roche, Biogen, and Axon; MO, SH and PO are co‐inventors of a patent handed for the measurement of beta‐synuclein. KGH reports speaker's honoraria, consulting fees, lecture honoraria and/or study grants from Abbott, Alexion, Amarin, AstraZeneca, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol‐Myers Squibb, Daiichi Sankyo, Edwards Lifesciences, Medronic, Novartis, Pfizer, Portola, Premier Research, Sanofi, SUN Pharma, and W.L. Gore and Associates. PUH reports grants from German Ministry of Research and Education, German Research Foundation, European Union, Federal Joint Committee (G‐BA) within the Innovationfond, Berlin Chamber of Physicians, German Parkinson Society, University Hospital Würzburg, Robert Koch Institute, German Heart Foundation, University Göttingen (within FIND‐AF [A Prospective, Randomised, Controlled Study to Determine the Detection of Atrial Fibrillation by Prolonged and Enhanced Holter Monitoring as Compared to Usual Care in Stroke Patients], supported by an unrestricted research grant to the University Göttingen from Boehringer‐Ingelheim), University Hospital Heidelberg (within Registry of Acute Stroke Under Novel Oral Anticoagulants [RASUNOA]‐prime, supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, Bristol‐Myers Squibb, Boehringer‐Ingelheim, Daiichi Sankyo), Charité–Universitätsmedizin Berlin (within MonDAFIS, supported by an unrestricted research grant to the Charité from Bayer), all outside the submitted work. PO received research support from the Cure Alzheimer Fund, ALS Association (24‐SGP‐691, 23‐PPG‐674‐2), ALS Finding a Cure, the Charcot Foundation, the DZNE Innovation‐to‐Application program and consulting fees from LifeArc and Fundamental Pharma. The other authors have nothing to declare.

Figures

FIGURE 1
FIGURE 1
Association between serum biomarkers and 3‐month mRS scores. (a) Spearman's correlations between serum biomarker levels and 3‐month mRS scores. (b) Serum biomarker levels in patients with good (mRS 0–2 or mRS unchanged compared to pre‐event mRS) vs. poor (mRS 3–6) functional outcome at 3‐month follow‐up. (c) Receiver operating characteristics (ROC) analysis for the discrimination between patients with good vs. poor 3‐month functional outcome assessing serum biomarkers. (d) Distribution of AIS patients with good vs. poor 3‐month functional outcome according to best biomarker cutoff values (found by maximizing the Youden index at ROC analysis). Patients were distinguished into two groups depending on whether the serum biomarker levels were above or below the cutoff value. ***p < 0.001.
FIGURE 2
FIGURE 2
Association between serum biomarkers and 3‐month all‐cause mortality. (a) Serum biomarker levels in AIS patients who survived vs. who did not survive at 3 months. (b) Receiver operating characteristics (ROC) analysis for the discrimination between patients who survived vs. who did not survive at 3 months by assessing serum biomarkers. (c) Distribution of patients who survived vs. who did not survive at 3 months according to best biomarker cutoff values (found by maximizing the Youden index at ROC analysis). Patients were distinguished into two groups depending on whether the serum biomarker levels were above or below the cutoff value. ***p < 0.001.
FIGURE 3
FIGURE 3
Association between serum biomarerks and clinical/radiological variables. (a) Spearman's correlations between serum biomarker levels and ASPECTS values on admission. (b) Serum biomarker levels in patients with admission ASPECTS <8 vs. ≥8 points. (c) Spearman's correlations between serum biomarkers and NIHSS score change within 24 h (admission NIHSS–NIHSS at 24 h). (d) Biomarker levels in patients with vs. without early neurological improvement (ENI) within 24 h (NIHSS change ≥4). ***p < 0.001.
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References

    1. Montellano FA, Ungethüm K, Ramiro L, et al. Role of blood‐based biomarkers in ischemic stroke prognosis: a systematic review. Stroke. 2021;52:543‐551. doi:10.1161/STROKEAHA.120.029232 - DOI - PubMed
    1. Khalil M, Teunissen CE, Lehmann S, et al. Neurofilaments as biomarkers in neurological disorders—towards clinical application. Nat Res. 2024;20:269‐287. doi:10.1038/s41582-024-00955-x - DOI - PubMed
    1. Abdelhak A, Foschi M, Abu‐Rumeileh S, et al. Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nat Rev Neurol. 2022;18(3):158‐172. doi:10.1038/s41582-021-00616-3 - DOI - PubMed
    1. Vollmuth C, Fiessler C, Montellano FA, et al. Incremental value of serum neurofilament light chain and glial fibrillary acidic protein as blood‐based biomarkers for predicting functional outcome in severe acute ischemic stroke. Eur Stroke J. 2024;9:751‐762. doi:10.1177/23969873241234436 - DOI - PMC - PubMed
    1. Oeckl P, Janelidze S, Halbgebauer S, et al. Higher plasma β‐synuclein indicates early synaptic degeneration in Alzheimer's disease. Alzheimers Dement. 2023;19(11):5095‐5102. doi:10.1002/alz.13103 - DOI - PubMed