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Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL
Chih-Hao Chen1,2, Yu-Wen Cheng3, Ya-Fang Chen4
1Stroke Center and Department of Neurology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 10055, Taiwan.
Insights
Plasma neurofilament light chain (NfL) can predict stroke in CADASIL patients, while glial fibrillary acidic protein (GFAP) may indicate cerebral hemorrhage risk. These biomarkers offer insights into disease progression and stroke prediction.
Area of Science:
- Neurology
- Biomarker Discovery
- Vascular Dementia Research
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a significant cause of stroke.
- Identifying reliable biomarkers for disease severity and stroke recurrence in CADASIL is crucial.
Purpose of the Study:
- To investigate plasma biomarkers for reflecting CADASIL disease severity.
- To assess the predictive value of plasma biomarkers for stroke recurrence in CADASIL patients.
Main Methods:
- Sixty-three CADASIL patients and 17 controls were analyzed.
- Plasma levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and UCHL1 were measured.
- Neuroimaging markers and Cox regression models were used to assess stroke prediction.
Main Results:
- CADASIL patients showed elevated plasma NfL, GFAP, and UCHL1 compared to controls.
- Plasma NfL and GFAP correlated with cerebral microbleeds and baseline stroke types.
- Higher baseline NfL predicted any incident stroke; higher GFAP predicted incident intracerebral hemorrhage (ICH).
Conclusions:
- Plasma NfL is a promising biomarker for monitoring incident stroke in CADASIL.
- Plasma GFAP may play a role in predicting cerebral hemorrhage in CADASIL patients.
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.
