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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 Common.EditSubmissionSteps.Transform.EquationText 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.
Keywords
CADASIL, stroke, intracerebral hemorrhage, biomarkers, neurofilament light chain, glial fibrillary acidic protein
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On 23 Mar, 2020
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On 23 Mar, 2020
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Posted 12 Feb, 2020
No comments provided
Review #2 received
Received 17 Mar, 2020
Editorial decision: Major Revision
On 17 Mar, 2020
Review #1 received
Received 01 Mar, 2020
Reviewer #3 agreed
On 19 Feb, 2020
Reviewer #2 agreed
On 18 Feb, 2020
Reviewer #1 agreed
On 12 Feb, 2020
Reviewers invited
Invitations sent on 12 Feb, 2020
Editor invited
On 11 Feb, 2020
Editor assigned
On 10 Feb, 2020
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Subject Areas
Neurobiology of Disease
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A new preprint design is coming!
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See the published version of this preprint at Journal of Neuroinflammation.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Sung-Chun Tang
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Journal of Neuroinflammation.
No community comments so far
Reviewer #2 agreed
On 25 Mar, 2020
Review #2 received
Received 25 Mar, 2020
Editor assigned
On 24 Mar, 2020
Reviewers invited
Invitations sent on 24 Mar, 2020
Reviewer #1 agreed
On 24 Mar, 2020
Submission checks complete
On 23 Mar, 2020
Editor invited
On 23 Mar, 2020
Version 1
Posted 12 Feb, 2020
No comments provided
Review #2 received
Received 17 Mar, 2020
Editorial decision: Major Revision
On 17 Mar, 2020
Review #1 received
Received 01 Mar, 2020
Reviewer #3 agreed
On 19 Feb, 2020
Reviewer #2 agreed
On 18 Feb, 2020
Reviewer #1 agreed
On 12 Feb, 2020
Reviewers invited
Invitations sent on 12 Feb, 2020
Editor invited
On 11 Feb, 2020
Editor assigned
On 10 Feb, 2020
Submission checks complete
On 09 Feb, 2020
First submitted
On 07 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Journal of Neuroinflammation.
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 Common.EditSubmissionSteps.Transform.EquationText 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.
Figure 1
Figure 2
Figure 3
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