BACKGROUND Stroke remains the most cumbersome disease burden in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study aimed to investigate whether plasma biomarkers can reflect disease severity and predict stroke recurrence in CADASIL patients. METHODS Sixty-three CADASIL patients (mean age 58.9 ± 9.3 years old, male 63%) from a multicenter registry and 17 controls were recruited. Plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), were measured using an ultra-sensitive single molecule array at baseline. Neuroimaging markers assessed included the Fazekas scale of white matter hyperintensity, numbers of lacunes, and cerebral microbleeds (CMBs). Cox proportional hazards regression models were applied to calculate the hazard ratio (HR) of plasma biomarkers at baseline for predicting incident stroke during follow-up. RESULTS Plasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. Among the CADASIL patients, both plasma NfL and GFAP levels positively correlated with the numbers of CMBs (r = 0.32 and r = 0.37, respectively; both p < 0.05). Higher plasma levels of NfL and GFAP were associated with any stroke (odds ratio 2.02, 95% confidence interval [CI] 1.06-3.87) and ICH (odds ratio 2.06, 95% CI 1.26-3.35) at baseline, respectively. Within a mean follow-up period of 3.1 ± 2.1 years, 10 patients (16%) had incident stroke and 6 of them were ICH. Higher baseline NfL (HR 1.93, 95% CI 1.19-3.13) predicted any incident stroke, whereas higher GFAP (HR 2.80, 95% CI 1.21-6.53) predicted incident ICH. CONCLUSIONS In CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may have a role in cerebral hemorrhage.

中文翻译：

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血浆神经丝轻链和神经胶质纤维酸性蛋白可预测CADASIL中风。

背景技术中风仍然是患有脑常染色体显性动脉病并伴有皮下梗塞和白质脑病（CADASIL）的患者中最麻烦的疾病负担。这项研究旨在调查血浆生物标志物是否可以反映CADASIL患者的疾病严重程度并预测中风复发。方法收集了来自多中心登记处的63名CADASIL患者（平均年龄58.9±9.3岁，男性63％）和17名对照。血浆生物标志物，即神经丝轻链（NfL），神经胶质纤维酸性蛋白（GFAP），tau和泛素羧基末端水解酶L1（UCHL1），在基线时使用超灵敏单分子阵列进行了测量。评估的神经影像标记物包括Fazekas量表的白质高信号，内腔数量和脑微出血（CMB）。应用Cox比例风险回归模型计算基线时血浆生物标志物的风险比（HR），以预测随访期间的中风事件。结果CADASIL患者的血浆NfL，GFAP和UCHL1水平显着高于对照组。在CADASIL患者中，血浆NfL和GFAP水平均与CMB数量呈正相关（分别为r = 0.32和r = 0.37；两者均p <0.05）。基线时，较高的NfL和GFAP血浆水平分别与任何卒中（比值2.02，95％置信区间[CI] 1.06-3.87）和ICH（比值2.06，95％CI 1.26-3.35）相关。在3.1±2.1年的平均随访期内，有10例患者（16％）发生了中风，其中6例为ICH。较高的基线NfL（HR 1.93，95％CI 1.19-3.13）预测发生任何中风，而较高的GFAP（HR 2.80，95％CI 1.21-6.53）则可预测发生ICH。结论在CADASIL患者中，血浆NfL可能是监测卒中的有前途的生物标志物，而GFAP可能在脑出血中起作用。