![]() ![]() Glial fibrillary acidic protein (GFAP), a brain-specific intermediate filament protein produced by astrocytes in response to brain injury, has been found to be a reliable marker for differentiating ICH and IS in patients with acute stroke. Fluid biomarkers are used for predicting the occurrences of IS and ICH in CADASIL patients however, they have not been well studied. In CADASIL patients, the neurofilament light chain (NfL) blood level has been found to correlate with the clinical and neuroimaging burdens and can predict their long-term disability and survival. ![]() Fluid biomarkers, especially blood-based, have the advantage of easy collection and repeat measurement over the relatively inconvenient neuroimaging tests. Studies have suggested that the brain parenchymal fraction or lacunes best correlate with disease severity and predict clinical worsening in CADASIL. Although the natural course of the disease has been extensively depicted, establishing reliable biomarkers to predict the occurrence of a vascular event including IS and ICH is crucial for developing an effective prevention strategy. Despite that intracerebral hemorrhage (ICH) is considered a rare manifestation in Caucasian CADASIL patients, a significant proportion of East Asian patients harboring p.R544C NOTCH3 mutation also suffer from ICH, and those with ICH are more prone to have recurrent stroke. ![]() Regarding the vascular events, ischemic stroke (IS) or transient ischemic attack is considered the cardinal features in CADASIL. In East Asian, p.R544C in exon 11 on NOTCH3 gene is the most prevalent hot spot mutation and accounted for more than 70% of the patients in their CADASIL cohorts. Neuroimaging features such as white matter hyperintensity (WMH), lacunes, and cerebral microbleeds (CMBs) may occur 10 to 15 years before the onset of stroke or cognitive decline. In CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may have a role in cerebral hemorrhage.Ĭerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease caused by mutations in the NOTCH3 gene, leading to devastating disease burden with stroke and vascular dementia in the affected adults. 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. 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 plasma levels of NfL and GFAP were associated with any stroke (odds ratio 2.02, 95% confidence interval 1.06–3.87) and ICH (odds ratio 2.06, 95% CI 1.26–3.35) at baseline, respectively. 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). Plasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. 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. Neuroimaging markers assessed included the Fazekas scale of white matter hyperintensity, numbers of lacunes, and cerebral microbleeds (CMBs). 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. Sixty-three CADASIL patients (mean age 58.9 ± 9.3 years old, male 63%) from a multicenter registry and 17 controls were recruited. This study aimed to investigate whether plasma biomarkers can reflect disease severity and predict stroke recurrence in CADASIL patients. Stroke remains the most cumbersome disease burden in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). ![]()
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