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已发表论文
血浆中分泌素 3A 作为脑小血管病认知障碍的潜在生物标志物
Authors Ma H, Li H, Fu X, Li X, Wei C, Ma A
Received 18 July 2025
Accepted for publication 25 October 2025
Published 5 November 2025 Volume 2025:18 Pages 6695—6708
DOI https://doi.org/10.2147/IJGM.S554075
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Dr Redoy Ranjan
Haoran Ma, Hong Li, Xinyi Fu, Xuening Li, Chenchen Wei, Aijun Ma
Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China
Correspondence: Aijun Ma; Chenchen Wei, Email drmaj@qdu.edu.cn; weichenchen2020@163.com
Background: Sema3A plays an essential role in the nervous system and is thought to regulate the entire course of the inflammatory response. This study aimed to explore the potential association between plasma Sema3A levels and cerebral small vessel disease (CSVD).
Methods: This study enrolled patients with recent small subcortical infarct (RSSI) and 100 healthy controls (HCs). Sema3A levels were measured during the acute phase (≤ 3 days) and the subacute phase (14– 30 days) of RSSI. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Brain magnetic resonance imaging (MRI) was used to evaluate CSVD imaging features. The study analyzed the association between Sema3A, CSVD imaging features, and cognitive impairment.
Results: Plasma Sema3A levels during the acute phase were markedly higher in RSSI patients than in HCs (p = 0.001), with an area under the receiver operating characteristic curve (AUC) of 0.715 (p < 0.01) for differentiating RSSIs from HCs. Levels were higher in the acute than the subacute phase (p < 0.001) but showed no difference between the subacute phase and HCs (p = 0.367).Within the RSSI group, acute-phase Sema3A levels were significantly higher in the CI subgroup (p < 0.001). A strong negative correlation was found between Sema3A and MoCA scores (r = − 0.459, p < 0.001). The AUC for distinguishing CI from non-cognitive impairment (NCI) was 0.793 (p < 0.01). In addition, acute-phase plasma Sema3A levels were notably elevated in patients with a high total CSVD burden (p < 0.001), and were positively correlated with the total imaging burden score (r = 0.469, p < 0.001). Mediation analysis showed that white matter hyperintensities (WMH) and lacunar infarcts (LI) significantly mediated the relationship between acute-phase Sema3A and CI (p < 0.001).
Conclusion: Plasma Sema3A levels during the acute phase were elevated in RSSI patients and were linked to cognitive impairment through the mediating roles of WMH and LI.
Keywords: cerebral small vessel disease, recent small subcortical infarct, cognitive impairment, total burden score, Sema3A
Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China
Correspondence: Aijun Ma; Chenchen Wei, Email drmaj@qdu.edu.cn; weichenchen2020@163.com
Background: Sema3A plays an essential role in the nervous system and is thought to regulate the entire course of the inflammatory response. This study aimed to explore the potential association between plasma Sema3A levels and cerebral small vessel disease (CSVD).
Methods: This study enrolled patients with recent small subcortical infarct (RSSI) and 100 healthy controls (HCs). Sema3A levels were measured during the acute phase (≤ 3 days) and the subacute phase (14– 30 days) of RSSI. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Brain magnetic resonance imaging (MRI) was used to evaluate CSVD imaging features. The study analyzed the association between Sema3A, CSVD imaging features, and cognitive impairment.
Results: Plasma Sema3A levels during the acute phase were markedly higher in RSSI patients than in HCs (p = 0.001), with an area under the receiver operating characteristic curve (AUC) of 0.715 (p < 0.01) for differentiating RSSIs from HCs. Levels were higher in the acute than the subacute phase (p < 0.001) but showed no difference between the subacute phase and HCs (p = 0.367).Within the RSSI group, acute-phase Sema3A levels were significantly higher in the CI subgroup (p < 0.001). A strong negative correlation was found between Sema3A and MoCA scores (r = − 0.459, p < 0.001). The AUC for distinguishing CI from non-cognitive impairment (NCI) was 0.793 (p < 0.01). In addition, acute-phase plasma Sema3A levels were notably elevated in patients with a high total CSVD burden (p < 0.001), and were positively correlated with the total imaging burden score (r = 0.469, p < 0.001). Mediation analysis showed that white matter hyperintensities (WMH) and lacunar infarcts (LI) significantly mediated the relationship between acute-phase Sema3A and CI (p < 0.001).
Conclusion: Plasma Sema3A levels during the acute phase were elevated in RSSI patients and were linked to cognitive impairment through the mediating roles of WMH and LI.
Keywords: cerebral small vessel disease, recent small subcortical infarct, cognitive impairment, total burden score, Sema3A