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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2020

01-12-2020 | Stroke | Research

Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL

Authors: Chih-Hao Chen, Yu-Wen Cheng, Ya-Fang Chen, Sung-Chun Tang, Jiann-Shing Jeng

Published in: Journal of Neuroinflammation | Issue 1/2020

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Abstract

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.
Literature
1.
Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG. Cadasil. The Lancet Neurology. 2009;8(7):643–53.PubMedCrossRef
2.
Lee YC, Liu CS, Chang MH, Lin KP, Fuh JL, Lu YC, et al. Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese. J Neurol. 2009;256(2):249–55.PubMedCrossRef
3.
Liao YC, Hsiao CT, Fuh JL, Chern CM, Lee WJ, Guo YC, et al. Characterization of CADASIL among the Han Chinese in Taiwan: distinct genotypic and phenotypic profiles. PloS one. 2015;10(8):e0136501.PubMedPubMedCentralCrossRef
4.
Chen CH, Tang SC, Cheng YW, Tsai HH, Chi NF, Sung PS, et al. Detrimental effects of intracerebral haemorrhage on patients with CADASIL harbouring NOTCH3 R544C mutation. J Neurol Neurosurg Psychiatry. 2019;90(7):841–3.PubMedCrossRef
5.
Tang SC, Chen YR, Chi NF, Chen CH, Cheng YW, Hsieh FI, et al. Prevalence and clinical characteristics of stroke patients with p.R544C NOTCH3 mutation in Taiwan. Annals of clinical and translational neurology. 2019;6(1):121–8.PubMedCrossRef
6.
Chabriat H, Herve D, Duering M, Godin O, Jouvent E, Opherk C, et al. Predictors of clinical worsening in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: prospective cohort study. Stroke. 2016;47(1):4–11.PubMedCrossRef
7.
Jouvent E, Duchesnay E, Hadj-Selem F, De Guio F, Mangin JF, Herve D, et al. Prediction of 3-year clinical course in CADASIL. Neurology. 2016;87(17):1787–95.PubMedPubMedCentralCrossRef
8.
Ling Y, De Guio F, Jouvent E, Duering M, Herve D, Guichard JP, et al. Clinical correlates of longitudinal MRI changes in CADASIL. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2019;39(7):1299–305.CrossRef
9.
Viswanathan A, Godin O, Jouvent E, O'Sullivan M, Gschwendtner A, Peters N, et al. Impact of MRI markers in subcortical vascular dementia: a multi-modal analysis in CADASIL. Neurobiol Aging. 2010;31(9):1629–36.PubMedCrossRef
10.
Duering M, Konieczny MJ, Tiedt S, Baykara E, Tuladhar AM, Leijsen EV, et al. Serum neurofilament light chain levels are related to small vessel disease burden. J Stroke. 2018;20(2):228–38.PubMedPubMedCentralCrossRef
11.
Gravesteijn G, Rutten JW, Verberk IMW, Bohringer S, Liem MK, van der Grond J, et al. Serum neurofilament light correlates with CADASIL disease severity and survival. Annals of clinical and translational neurology. 2019;6(1):46–56.PubMedCrossRef
12.
Zhang J, Zhang CH, Lin XL, Zhang Q, Wang J, Shi SL. Serum glial fibrillary acidic protein as a biomarker for differentiating intracerebral hemorrhage and ischemic stroke in patients with symptoms of acute stroke: a systematic review and meta-analysis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2013;34(11):1887–92.CrossRef
13.
Perry LA, Lucarelli T, Penny-Dimri JC, McInnes MD, Mondello S, Bustamante A, et al. Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage: systematic review and meta-analysis of diagnostic test accuracy. International journal of stroke : official journal of the International Stroke Society. 2019;14(4):390–9.CrossRef
14.
Ren C, Kobeissy F, Alawieh A, Li N, Li N, Zibara K, et al. Assessment of serum UCH-L1 and GFAP in acute stroke patients. Scientific reports. 2016;6:24588.PubMedPubMedCentralCrossRef
15.
Ren C, Zoltewicz S, Guingab-Cagmat J, Anagli J, Gao M, Hafeez A, et al. Different expression of ubiquitin C-terminal hydrolase-L1 and alphaII-spectrin in ischemic and hemorrhagic stroke: potential biomarkers in diagnosis. Brain research. 2013;1540:84–91.PubMedCrossRef
16.
Bitsch A, Horn C, Kemmling Y, Seipelt M, Hellenbrand U, Stiefel M, et al. Serum tau protein level as a marker of axonal damage in acute ischemic stroke. European neurology. 2002;47(1):45–51.PubMedCrossRef
17.
De Vos A, Bjerke M, Brouns R, De Roeck N, Jacobs D, Van den Abbeele L, et al. Neurogranin and tau in cerebrospinal fluid and plasma of patients with acute ischemic stroke. BMC neurology. 2017;17(1):170.PubMedPubMedCentralCrossRef
18.
DiMeglio M, Furey W, Hajj J, Lindekens J, Patel S, Acker M, et al. Observational study of long-term persistent elevation of neurodegeneration markers after cardiac surgery. Scientific reports. 2019;9(1):7177.PubMedPubMedCentralCrossRef
19.
Thelin E, Al Nimer F, Frostell A, Zetterberg H, Blennow K, Nystrom H, et al. A Serum protein biomarker panel improves outcome prediction in human traumatic brain injury. J Neurotrauma. 2019.
20.
Heller C, Foiani MS, Moore K, Convery R, Bocchetta M, Neason M, et al. Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia. Journal of Neurology, Neurosurgery & Psychiatry. 2020;91(3):263–70.CrossRef
21.
McCrea M, Broglio SP, McAllister TW, Gill J, Giza CC, Huber DL, et al. Association of blood biomarkers with acute sport-related concussion in collegiate athletes: findings from the NCAA and Department of Defense CARE Consortium. JAMA Netw Open. 2020;3(1):e1919771.PubMedPubMedCentralCrossRef
22.
Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. The Lancet Neurology. 2010;9(7):689–701.PubMedCrossRef
23.
Kim KW, MacFall JR, Payne ME. Classification of white matter lesions on magnetic resonance imaging in elderly persons. Biological psychiatry. 2008;64(4):273–80.PubMedPubMedCentralCrossRef
24.
Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurology. 2013;12(8):822–38.PubMedPubMedCentralCrossRef
25.
Gregoire SM, Chaudhary UJ, Brown MM, Yousry TA, Kallis C, Jager HR, et al. The Microbleed Anatomical Rating Scale (MARS): reliability of a tool to map brain microbleeds. Neurology. 2009;73(21):1759–66.PubMedCrossRef
26.
Dichgans M, Mayer M, Uttner I, Bruning R, Muller-Hocker J, Rungger G, et al. The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Annals of neurology. 1998;44(5):731–9.PubMedCrossRef
27.
Desmond DW, Moroney JT, Lynch T, Chan S, Chin SS, Mohr JP. The natural history of CADASIL: a pooled analysis of previously published cases. Stroke. 1999;30(6):1230–3.PubMedCrossRef
28.
Ling Y, De Guio F, Duering M, Jouvent E, Herve D, Godin O, et al. Predictors and clinical impact of incident lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke. 2017;48(2):283–9.PubMedCrossRef
29.
Puy L, De Guio F, Godin O, Duering M, Dichgans M, Chabriat H, et al. Cerebral microbleeds and the risk of incident ischemic stroke in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). Stroke. 2017;48(10):2699–703.PubMedCrossRef
30.
Disanto G, Barro C, Benkert P, Naegelin Y, Schadelin S, Giardiello A, et al. Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Annals of neurology. 2017;81(6):857–70.PubMedPubMedCentralCrossRef
31.
Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association between longitudinal plasma neurofilament light and neurodegeneration in patients with Alzheimer disease. JAMA neurology. 2019;76(7):791–9.PubMedCrossRef
32.
Lin CH, Li CH, Yang KC, Lin FJ, Wu CC, Chieh JJ, et al. Blood NfL: A biomarker for disease severity and progression in Parkinson disease. Neurology. 2019;93(11):e1104–e11.PubMedCrossRef
33.
Uphaus T, Bittner S, Groschel S, Steffen F, Muthuraman M, Wasser K, et al. NfL (neurofilament light chain) levels as a predictive marker for long-term outcome after ischemic stroke. Stroke. 2019;50(11):3077–84.PubMedCrossRef
34.
Lee JS, Ko K, Oh JH, Park JH, Lee HK, Floriolli D, et al. Cerebral microbleeds, hypertension, and intracerebral hemorrhage in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Frontiers in neurology. 2017;8:203.PubMedPubMedCentralCrossRef
35.
Katsanos AH, Makris K, Stefani D, Koniari K, Gialouri E, Lelekis M, et al. Plasma glial fibrillary acidic protein in the differential diagnosis of intracerebral hemorrhage. Stroke. 2017;48(9):2586–8.PubMedCrossRef
36.
Yue JK, Yuh EL, Korley FK, Winkler EA, Sun X, Puffer RC, et al. Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study. The Lancet Neurology. 2019;18(10):953–61.PubMedCrossRef
37.
Hase Y, Chen A, Bates LL, Craggs LJL, Yamamoto Y, Gemmell E, et al. Severe white matter astrocytopathy in CADASIL. Brain pathology (Zurich, Switzerland). 2018;28(6):832-43.
38.
Graham SH, Liu H. Life and death in the trash heap: the ubiquitin proteasome pathway and UCHL1 in brain aging, neurodegenerative disease and cerebral ischemia. Ageing Research Reviews. 2017;34:30–8.PubMedCrossRef
39.
Liu H, Povysheva N, Rose ME, Mi Z, Banton JS, Li W, et al. Role of UCHL1 in axonal injury and functional recovery after cerebral ischemia. Proceedings of the National Academy of Sciences. 2019;116(10):4643–50.CrossRef
40.
Lee YC, Chung CP, Chang MH, Wang SJ, Liao YC. NOTCH3 cysteine-altering variant is an important risk factor for stroke in the Taiwanese population. Neurology. 2020;94(1):e87–96.PubMedCrossRef
Metadata
Title
Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL
Authors
Chih-Hao Chen
Yu-Wen Cheng
Ya-Fang Chen
Sung-Chun Tang
Jiann-Shing Jeng
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-020-01813-5

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