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Neurological Sciences

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26.11.2021 | Original Article

Blood–brain barrier dysfunction and myelin basic protein in survival of amyotrophic lateral sclerosis with or without frontotemporal dementia

verfasst von: Jin-Yue Li, Zheng-Yi Cai, Xiao-Han Sun, Dong-chao Shen, Xun-Zhe Yang, Ming-Sheng Liu, Li-Ying Cui

Erschienen in: Neurological Sciences | Ausgabe 5/2022

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Abstract

Objective

We aim to investigate blood–brain barrier (BBB) dysfunction and myelin basic protein (MBP) in amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD) and further determine the effect of these factors on the survival of ALS.

Methods

This was a retrospective study of 113 ALS patients, 12 ALS-FTD patients, and 40 disease controls hospitalized between September 2013 and October 2020. CSF parameters including total protein (TP), albumin (Alb), immunoglobulin-G (IgG), and MBP were collected and compared between groups. The CSF-TP, CSF-Alb, CSF-IgG, and CSF/serum quotients of Alb and IgG (Q_Alb, Q_IgG) were used to reflect the BBB status. Patients were followed up until December 2020. Cox regression and Kaplan–Meier method were used for survival analysis.

Results

The CSF-TP, CSF-Alb, and CSF-IgG concentrations were significantly higher in patients than controls (p < 0.01). Increased CSF-TP and CSF-IgG was found in 45 (39.8%) and 27 (23.9%) ALS patients, while in 7 (58.3%) and 5 (41.7%) ALS-FTD patients. The level of CSF-Alb, CSF-IgG, and CSF-MBP were significantly higher in patients with ALS-FTD than ALS. MBP showed a moderate accuracy in the distinction between ALS-FTD and ALS (AUC = 0.715 ± 0.101). No difference in MBP was found between patients and controls. Kaplan–Meier analysis indicated that a higher CSF-TP, CSF-IgG, Q_IgG, or Q_Alb was significantly associated with shorter survival. Cox regression model showed that CSF-TP, CSF-IgG, and Q_IgG were independent predictors of survival.

Conclusion

Our findings suggested that BBB dysfunction was more prominent in ALS-FTD than ALS and associated with a worse prognosis. Further studies are needed to determine the role of CSF-MBP as a biomarker in ALS.

Nur mit Berechtigung zugänglich

Ferrari R, Kapogiannis D, Huey ED, Momeni P (2011) FTD and ALS: a tale of two diseases. Curr Alzheimer Res 8:273–94. https://doi.org/10.2174/156720511795563700CrossRefPubMedPubMedCentral

Sweeney MD, Sagare AP, Zlokovic BV (2018) Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol 14:133–150. https://doi.org/10.1038/nrneurol.2017.188CrossRefPubMedPubMedCentral

Winkler EA, Sengillo JD, Sagare AP, Zhao Z, Ma Q, Zuniga E, Wang Y, Zhong Z, Sullivan JS, Griffin JH, Cleveland DW, Zlokovic BV (2014) Blood-spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice. Proc Natl Acad Sci USA 111:E1035-42. https://doi.org/10.1073/pnas.1401595111CrossRefPubMedPubMedCentral

Sasaki S (2015) Alterations of the blood-spinal cord barrier in sporadic amyotrophic lateral sclerosis. Neuropathology 35:518–28. https://doi.org/10.1111/neup.12221CrossRefPubMed

Niebroj-Dobosz I, Janik P, Sokolowska B, Kwiecinski H (2010) Matrix metalloproteinases and their tissue inhibitors in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Eur J Neurol 17:226–31. https://doi.org/10.1111/j.1468-1331.2009.02775.xCrossRefPubMed

Saul J, Hutchins E, Reiman R, Saul M, Ostrow LW, Harris BT, Van Keuren-Jensen K, Bowser R, Bakkar N (2020) Global alterations to the choroid plexus blood-CSF barrier in amyotrophic lateral sclerosis. Acta Neuropathol Commun 8:92. https://doi.org/10.1186/s40478-020-00968-9CrossRefPubMedPubMedCentral

Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV (2019) Blood-brain barrier: from physiology to disease and back. Physiol Rev 99:21–78. https://doi.org/10.1152/physrev.00050.2017CrossRefPubMed

Clarke BE, Patani R (2020) The microglial component of amyotrophic lateral sclerosis. Brain 143:3526–3539. https://doi.org/10.1093/brain/awaa309CrossRefPubMedPubMedCentral

Pehar M, Harlan BA, Killoy KM, Vargas MR (2017) Role and Therapeutic Potential of Astrocytes in Amyotrophic Lateral sclerosis. Curr Pharm Des 23:5010–5021. https://doi.org/10.2174/1381612823666170622095802CrossRefPubMedPubMedCentral

10.

Boggs JM (2006) Myelin basic protein: a multifunctional protein. Cell Mol Life Sci 63:1945–61. https://doi.org/10.1007/s00018-006-6094-7CrossRefPubMed

11.

Vassall KA, Bamm VV, Harauz G (2015) MyelStones: the executive roles of myelin basic protein in myelin assembly and destabilization in multiple sclerosis. Biochem J 472:17–32. https://doi.org/10.1042/BJ20150710CrossRefPubMed

12.

Bohnert S, Wirth C, Schmitz W, Trella S, Monoranu CM, Ondruschka B, Bohnert M (2021) Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury. Int J Legal Med. https://doi.org/10.1007/s00414-021-02606-y

13.

Zavialova MG, Shevchenko VE, Nikolaev EN, Zgoda VG (2017) Is myelin basic protein a potential biomarker of brain cancer? Eur J Mass Spectrom (Chichester) 23:192–196. https://doi.org/10.1177/1469066717719810CrossRef

14.

Brooks BR, Miller RG, Swash M, Munsat TL (2000) World Federation of Neurology Research Group on Motor Neuron D. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:293–9. https://doi.org/10.1080/146608200300079536CrossRefPubMed

15.

Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EG, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini ML, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134:2456–77. https://doi.org/10.1093/brain/awr179CrossRefPubMedPubMedCentral

16.

Cui B, Cui L, Gao J, Liu M, Li X, Liu C, Ma J, Fang J (2015) Cognitive impairment in Chinese patients with sporadic amyotrophic lateral sclerosis. PLoS One 10:e0137921. https://doi.org/10.1371/journal.pone.0137921CrossRefPubMedPubMedCentral

17.

Freedman MS, Thompson EJ, Deisenhammer F, Giovannoni G, Grimsley G, Keir G, Ohman S, Racke MK, Sharief M, Sindic CJ, Sellebjerg F, Tourtellotte WW (2005) Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol 62:865–70. https://doi.org/10.1001/archneur.62.6.865CrossRefPubMed

18.

Glasner H (1975) Barrier impairment and immune reaction in the cerebrospinal fluid. Eur Neurol 13:304–14. https://doi.org/10.1159/000114685CrossRefPubMed

19.

Meucci G, Rossi G, Bettini R, Montanaro D, Gironelli L, Voci L, Bianchi F (1993) Laser nephelometric evaluation of albumin, IgG and alpha 2-macroglobulin: applications to the study of alterations of the blood-brain barrier. J Neurol Sci 118:73–8. https://doi.org/10.1016/0022-510x(93)90248-wCrossRefPubMed

20.

Stevens A, Weller M, Wietholter H (1993) A characteristic ganglioside antibody pattern in the CSF of patients with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 56:361. https://doi.org/10.1136/jnnp.56.4.361CrossRefPubMedPubMedCentral

21.

Apostolski S, Nikolic J, Bugarski-Prokopljevic C, Miletic V, Pavlovic S, Filipovic S (1991) Serum and CSF immunological findings in ALS. Acta Neurol Scand 83:96–8. https://doi.org/10.1111/j.1600-0404.1991.tb04656.xCrossRefPubMed

22.

Zhao X, Yang F, Wang H, Cui F, Li M, Sun B, Li Y, Sun Q, He Z, Li Y, Huang X (2020) The increase in CSF total protein and immunoglobulins in Chinese patients with sporadic amyotrophic lateral sclerosis: A retrospective study. J Neurol Sci 414:116840. https://doi.org/10.1016/j.jns.2020.116840CrossRefPubMed

23.

Leonardi A, Abbruzzese G, Arata L, Cocito L, Vische M (1984) Cerebrospinal fluid (CSF) findings in amyotrophic lateral sclerosis. J Neurol 231:75–8. https://doi.org/10.1007/BF00313720CrossRefPubMed

24.

Ticozzi N, Tiloca C, Mencacci NE, Morelli C, Doretti A, Rusconi D, Colombrita C, Sangalli D, Verde F, Finelli P, Messina S, Ratti A, Silani V (2013) Oligoclonal bands in the cerebrospinal fluid of amyotrophic lateral sclerosis patients with disease-associated mutations. J Neurol 260:85–92. https://doi.org/10.1007/s00415-012-6589-0CrossRefPubMed

25.

Lu CH, Allen K, Oei F, Leoni E, Kuhle J, Tree T, Fratta P, Sharma N, Sidle K, Howard R, Orrell R, Fish M, Greensmith L, Pearce N, Gallo V, Malaspina A (2016) Systemic inflammatory response and neuromuscular involvement in amyotrophic lateral sclerosis. Neurol Neuroimmunol Neuroinflamm 3:e244. https://doi.org/10.1212/NXI.0000000000000244CrossRefPubMedPubMedCentral

26.

Lu CH, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N, Giovannoni G, Fratta P, Sidle K, Fish M, Orrell R, Howard R, Talbot K, Greensmith L, Kuhle J, Turner MR, Malaspina A (2015) Neurofilament light chain: a prognostic biomarker in amyotrophic lateral sclerosis. Neurology 84:2247–57. https://doi.org/10.1212/WNL.0000000000001642CrossRefPubMedPubMedCentral

27.

Chelstowska B, Kuzma-Kozakiewicz M (2020) Biochemical parameters in determination of nutritional status in amyotrophic lateral sclerosis. Neurol Sci 41:1115–1124. https://doi.org/10.1007/s10072-019-04201-xCrossRefPubMed

28.

Hansson O, Janelidze S, Hall S, Magdalinou N, Lees AJ, Andreasson U, Norgren N, Linder J, Forsgren L, Constantinescu R, Zetterberg H, Blennow K, Fs Swedish Bio (2017) Blood-based NfL: a biomarker for differential diagnosis of parkinsonian disorder. Neurology 88:930–937. https://doi.org/10.1212/WNL.0000000000003680CrossRefPubMedPubMedCentral

29.

Varhaug KN, Torkildsen O, Myhr KM, Vedeler CA (2019) Neurofilament light chain as a biomarker in multiple sclerosis. Front Neurol 10:338. https://doi.org/10.3389/fneur.2019.00338CrossRefPubMedPubMedCentral

30.

Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K (2019) Association between longitudinal plasma neurofilament light and neurodegeneration in patients with Alzheimer disease. JAMA Neurol 76:791–799. https://doi.org/10.1001/jamaneurol.2019.0765CrossRefPubMedPubMedCentral

31.

Thouvenot E, Demattei C, Lehmann S, Maceski-Maleska A, Hirtz C, Juntas-Morales R, Pageot N, Esselin F, Alphandery S, Vincent T, Camu W (2020) Serum neurofilament light chain at time of diagnosis is an independent prognostic factor of survival in amyotrophic lateral sclerosis. Eur J Neurol 27:251–257. https://doi.org/10.1111/ene.14063CrossRefPubMed

32.

Brodovitch A, Boucraut J, Delmont E, Parlanti A, Grapperon AM, Attarian S, Verschueren A (2021) Combination of serum and CSF neurofilament-light and neuroinflammatory biomarkers to evaluate ALS. Sci Rep 11:703. https://doi.org/10.1038/s41598-020-80370-6CrossRefPubMedPubMedCentral

33.

Coatti GC, Frangini M, Valadares MC, Gomes JP, Lima NO, Cavacana N, Assoni AF, Pelatti MV, Birbrair A, de Lima ACP, Singer JM, Rocha FMM, Da Silva GL, Mantovani MS, Macedo-Souza LI, Ferrari MFR, Zatz M (2017) Pericytes extend survival of ALS SOD1 mice and induce the expression of antioxidant enzymes in the murine model and in IPSCs derived neuronal cells from an ALS patient. Stem Cell Rev Rep 13:686–698. https://doi.org/10.1007/s12015-017-9752-2CrossRefPubMed

34.

Almutairi MM, Gong C, Xu YG, Chang Y, Shi H (2016) Factors controlling permeability of the blood-brain barrier. Cell Mol Life Sci 73:57–77. https://doi.org/10.1007/s00018-015-2050-8CrossRefPubMed

35.

Caroppo P, Le Ber I, Camuzat A, Clot F, Naccache L, Lamari F, De Septenville A, Bertrand A, Belliard S, Hannequin D, Colliot O, Brice A (2014) Extensive white matter involvement in patients with frontotemporal lobar degeneration: think progranulin. JAMA Neurol 71:1562–6. https://doi.org/10.1001/jamaneurol.2014.1316CrossRefPubMed

36.

Sudre CH, Bocchetta M, Heller C, Convery R, Neason M, Moore KM, Cash DM, Thomas DL, Woollacott IOC, Foiani M, Heslegrave A, Shafei R, Greaves C, van Swieten J, Moreno F, Sanchez-Valle R, Borroni B, Laforce R Jr, Masellis M, Tartaglia MC, Graff C, Galimberti D, Rowe JB, Finger E, Synofzik M, Vandenberghe R, de Mendonca A, Tagliavini F, Santana I, Ducharme S, Butler C, Gerhard A, Levin J, Danek A, Frisoni GB, Sorbi S, Otto M, Zetterberg H, Ourselin S, Cardoso MJ, Rohrer JD, On behalf of G, (2019) White matter hyperintensities in progranulin-associated frontotemporal dementia: a longitudinal GENFI study. Neuroimage Clin 24:102077. https://doi.org/10.1016/j.nicl.2019.102077CrossRefPubMedPubMedCentral

37.

Sudre CH, Bocchetta M, Cash D, Thomas DL, Woollacott I, Dick KM, van Swieten J, Borroni B, Galimberti D, Masellis M, Tartaglia MC, Rowe JB, Graff C, Tagliavini F, Frisoni G, Laforce R Jr, Finger E, de Mendonca A, Sorbi S, Ourselin S, Cardoso MJ, Rohrer JD, Genetic Ftd Initiative G (2017) White matter hyperintensities are seen only in GRN mutation carriers in the GENFI cohort. Neuroimage Clin 15:171–180. https://doi.org/10.1016/j.nicl.2017.04.015CrossRefPubMedPubMedCentral

38.

Hiji M, Takahashi T, Fukuba H, Yamashita H, Kohriyama T, Matsumoto M (2008) White matter lesions in the brain with frontotemporal lobar degeneration with motor neuron disease: TDP-43-immunopositive inclusions co-localize with p62, but not ubiquitin. Acta Neuropathol 116(183):91. https://doi.org/10.1007/s00401-008-0402-2CrossRef

39.

Kim S, Chung AY, Na JE, Lee SJ, Jeong SH, Kim E, Sun W, Rhyu IJ (1921) Park HC 2019 Myelin degeneration induced by mutant superoxide dismutase 1 accumulation promotes amyotrophic lateral sclerosis. Glia 67:1910. https://doi.org/10.1002/glia.23669CrossRef

40.

Lu Y, Tang C, Zhu L, Li J, Liang H, Zhang J, Xu R (2016) The overexpression of TDP-43 protein in the neuron and oligodendrocyte cells causes the progressive motor neuron degeneration in the SOD1 G93A transgenic mouse model of amyotrophic lateral sclerosis. Int J Biol Sci 12:1140–9. https://doi.org/10.7150/ijbs.15938CrossRefPubMedPubMedCentral

41.

Lorente Pons A, Higginbottom A, Cooper-Knock J, Alrafiah A, Alofi E, Kirby J, Shaw PJ, Wood JD, Highley JR (2020) Oligodendrocyte pathology exceeds axonal pathology in white matter in human amyotrophic lateral sclerosis. J Pathol 251:262–271. https://doi.org/10.1002/path.5455CrossRefPubMed

Titel: Blood–brain barrier dysfunction and myelin basic protein in survival of amyotrophic lateral sclerosis with or without frontotemporal dementia
verfasst von: Jin-Yue Li
Zheng-Yi Cai
Xiao-Han Sun
Dong-chao Shen
Xun-Zhe Yang
Ming-Sheng Liu
Li-Ying Cui
Publikationsdatum: 26.11.2021
Verlag: Springer International Publishing
Erschienen in: Neurological Sciences / Ausgabe 5/2022
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-021-05731-z

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Blood–brain barrier dysfunction and myelin basic protein in survival of amyotrophic lateral sclerosis with or without frontotemporal dementia