Serum levels of neurofilament light chain (NfL) and glial fibrillary acid protein (GFAP) in patients with asymptomatic and symptomatic carotid artery stenosis.

Objective: The treatment of carotid artery stenosis (CAS) for stroke prevention is a matter of debate due to conflicting data, missing recent data, and advances in medical treatment options but also in interventional techniques and surgery. Therefore, the establishment of an easily available marker for brain damage might be a key tool in this patient group to guide treatment. Methods: A retrospective cross-sectional study was conducted leveraging a vascular surgery biobank of 95 patients aged 60 to 80 years. Serum neurofilament light chain (sNfL) and serum glial fibrillary acid protein (sGFAP) were evaluated using highly sensitive electrochemiluminescence immunoassays and z-scores. Discriminatory performance was assessed to differentiate between 19 symptomatic and 76 asymptomatic patients with CAS and their correlation with the degree of stenosis according to ultrasound-based North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Results: SNfL levels were markedly elevated in symptomatic compared with asymptomatic patients (median 17.4 vs 3.8 pg/mL; Conclusions: The study provides evidence of increased sNfL in symptomatic vs asymptomatic CAS and, of note, of ongoing neuronal or glial damage in some patients with clinically asymptomatic CAS, with a positive correlation between sNfL and the degree of CAS. sNfL is a promising and already accessible blood biomarker that may guide therapeutic decisions in this patient population. The role of sGFAP remains elusive and must be evaluated in larger studies. Clinical Relevance: The CREST-2 trial has recently highlighted the high efficacy of intensive medical management in asymptomatic carotid artery stenosis (CAS), making the selection of patients for revascularization increasingly complex. Our study addresses this challenge by evaluating serum neurofilament light chain (sNfL) and serum glial fibrillary acid protein (sGFAP) as an objective biomarker for neuronal injury. Using individualized z-scores, we demonstrate that sNfL effectively differentiates symptomatic status (area under the curve = 0.828) and significantly correlates with the degree of stenosis in asymptomatic cohorts. These results suggest that sNfL can detect subclinical "silent" damage, providing a valuable biological tool to pinpoint high-risk patients who may require intervention beyond medical therapy alone. This represents a significant step toward personalized stroke prevention and refined risk stratification in the highly debated field of CAS management.