Serum glial fibrillary acidic protein is sensitive to acute but not chronic tissue damage in cerebral small vessel disease

Background Serum glial fibrillary acidic protein (sGFAP) has been proposed as a biomarker in various neurological diseases but has not yet been systematically investigated in patients with cerebral small vessel disease (CSVD). We explored whether sGFAP levels are increased in stroke patients with MRI-confirmed recent small subcortical infarcts (RSSI) and analyzed the subsequent course and determinants of sGFAP longitudinally. Methods In a prospectively-collected cohort of stroke patients with a single RSSI (n = 101, mean age: 61 years, 73% men), we analyzed brain MRI and sGFAP using a SIMOA assay at baseline and at 3- and 15-months post-stroke. Community-dwelling age- and sex-matched individuals (n = 51) served as controls. Results RSSI patients had higher baseline sGFAP levels compared to controls (median: 187.4 vs. 118.3 pg/ml, p < 0.001), with no influence of the time from stroke symptom onset to baseline blood sampling (median 5 days, range 1-13). At the 3- and 15-months follow-up, sGFAP returned to control levels. While baseline sGFAP correlated with larger infarct size (r(s) = 0.28, p = 0.01), neither baseline nor follow-up sGFAP levels were associated with chronic CSVD-related lesions (white matter hyperintensities, lacunes, microbleeds) after adjusting for age, sex and hypertension. Furthermore, sGFAP levels did not relate to the occurrence of new vascular brain lesions on follow-up MRI. Conclusions sGFAP is increased in patients with CSVD-related stroke and correlates with the size of the RSSI. However, sGFAP levels were not related to chronic neuroimaging features or progression of CSVD, suggesting that sGFAP is sensitive to acute but not chronic cerebrovascular tissue changes in this condition.

Automated summary

This study found that serum glial fibrillary acidic protein (sGFAP) levels are increased in stroke patients with cerebral small vessel disease (CSVD)-related stroke, and are correlated with the size of the stroke. However, sGFAP levels are not associated with chronic CSVD-related lesions or progression, suggesting that sGFAP is sensitive to acute but not chronic cerebrovascular tissue changes in this condition.