Abstract
Neuroinflammation is a hallmark of several neurodegenerative diseases including multiple sclerosis, Alzheimer’s, and Parkinson’s disease. Recent evidence shows that chronic activation of the immune system could be used to pinpoint the onset and progression of these diseases in concomitant analysis with disease-specific signatures. Tumor necrosis factor alpha (TNFα) a pleiotropic proinflammatory cytokine with distinct functions in homeostasis and disease pathogenesis, has been recognized as a potential biomarker for several neurological disorders. In the context of neuroinflammation and neurodegeneration, here we describe a method for quantitative detection of TNFα, in clinically relevant body fluids, based on an ultrasensitive impedimetric system.
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References
Medzhitov R (2008) Origin and physiological roles of inflammation. Nature 454:428–435. https://doi.org/10.1038/nature07201
DiSabato DJ, Quan N, Godbout JP (2016) Neuroinflammation: the devil is in the details. J Neurochem 139:136–153. https://doi.org/10.1111/jnc.13607
Norris GT, Kipnis J (2019) Immune cells and CNS physiology: microglia and beyond. J Exp Med 216:60–70. https://doi.org/10.1084/jem.20180199
Voet S, Prinz M, van Loo G (2019) Microglia in central nervous system inflammation and multiple sclerosis pathology. Trends Mol Med 25:112–123. https://doi.org/10.1016/j.molmed.2018.11.005
Abreu CM, Soares-dos-Reis R, Melo PN, Relvas JB, Guimarães J, Sá MJ, Cruz AP, Mendes Pinto I (2018) Emerging biosensing technologies for neuroinflammatory and neurodegenerative disease diagnostics. Front Mol Neurosci 11:164. https://doi.org/10.3389/fnmol.2018.00164
Çomoǧlu SS, Güven H, Acar M, Öztürk G, Koçer B (2013) Tear levels of tumor necrosis factor-alpha in patients with Parkinson’s disease. Neurosci Lett 553:63–67. https://doi.org/10.1016/j.neulet.2013.08.019
D’Ambrosio A, Pontecorvo S, Colasanti T, Zamboni S, Francia A, Margutti P (2015) Peripheral blood biomarkers in multiple sclerosis. Autoimmun Rev 14:1097–1110. https://doi.org/10.1016/j.autrev.2015.07.014
Housley WJ, Pitt D, Hafler DA (2015) Biomarkers in multiple sclerosis. Clin Immunol 161:51–58. https://doi.org/10.1016/j.clim.2015.06.015
Kothur K, Wienholt L, Brilot F, Dale RC (2016) CSF cytokines/chemokines as biomarkers in neuroinflammatory CNS disorders: a systematic review. Cytokine 77:227–237. https://doi.org/10.1016/j.cyto.2015.10.001
Novakova L, Axelsson M, Khademi M, Zetterberg H, Blennow K, Malmeström C, Piehl F, Olsson T, Lycke J (2017) Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing-remitting multiple sclerosis. J Neurochem 141:296–304. https://doi.org/10.1111/jnc.13881
Zetterberg H (2017) Fluid biomarkers for microglial activation and axonal injury in multiple sclerosis. Acta Neurol Scand 136:15–17. https://doi.org/10.1111/ane.12845
Rocha NP, De Miranda AS, Teixeira AL (2015) Insights into neuroinflammation in Parkinson’s disease: from biomarkers to anti-inflammatory based therapies. Biomed Res Int 2015:1–12. https://doi.org/10.1155/2015/628192
Brockmann K, Schulte C, Schneiderhan-Marra N, Apel A, Pont-Sunyer C, Vilas D, Ruiz-Martinez J, Langkamp M, Corvol J-C, Cormier F, Knorpp T, Joos TO, Bernard A, Gasser T, Marras C, Schüle B, Aasly JO, Foroud T, Marti-Masso JF, Brice A, Tolosa E, Berg D, Maetzler W (2017) Inflammatory profile discriminates clinical subtypes in LRRK2-associated Parkinson’s disease. Eur J Neurol 24:427–4e6. https://doi.org/10.1111/ene.13223
Andersen AD, Binzer M, Stenager E, Gramsbergen JB (2017) Cerebrospinal fluid biomarkers for Parkinson’s disease—a systematic review. Acta Neurol Scand 135:34–56. https://doi.org/10.1111/ane.12590
Olsson B, Lautner R, Andreasson U, Öhrfelt A, Portelius E, Bjerke M, Hölttä M, Rosén C, Olsson C, Strobel G, Wu E, Dakin K, Petzold M, Blennow K, Zetterberg H (2016) CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol 15:673–684. https://doi.org/10.1016/S1474-4422(16)00070-3
Popp J, Oikonomidi A, Tautvydaitė D, Dayon L, Bacher M, Migliavacca E, Henry H, Kirkland R, Severin I, Wojcik J, Bowman GL (2017) Markers of neuroinflammation associated with Alzheimer’s disease pathology in older adults. Brain Behav Immun 62:203–211. https://doi.org/10.1016/j.bbi.2017.01.020
Brosseron F, Krauthausen M, Kummer M, Heneka MT (2014) Body fluid cytokine levels in mild cognitive impairment and Alzheimer’s disease: a comparative overview. Mol Neurobiol 50:534–544. https://doi.org/10.1007/s12035-014-8657-1
Delaby C, Gabelle A, Blum D, Schraen-Maschke S, Moulinier A, Boulanghien J, Séverac D, Buée L, Rème T, Lehmann S (2015) Central nervous system and peripheral inflammatory processes in Alzheimer’s disease: biomarker profiling approach. Front Neurol 6:1–11. https://doi.org/10.3389/fneur.2015.00181
Yu S, Liu Y-P, Liu Y-H, Jiao S-S, Liu L, Wang Y-J, Fu W-L (2016) Diagnostic utility of VEGF and soluble CD40L levels in serum of Alzheimer’s patients. Clin Chim Acta 453:154–159. https://doi.org/10.1016/j.cca.2015.12.018
Hesse R, Wahler A, Gummert P, Kirschmer S, Otto M, Tumani H, Lewerenz J, Schnack C, von Arnim CAF (2016) Decreased IL-8 levels in CSF and serum of AD patients and negative correlation of MMSE and IL-1β. BMC Neurol 16:185. https://doi.org/10.1186/s12883-016-0707-z
Majumder V, Gregory JM, Barria MA, Green A, Pal S (2018) TDP-43 as a potential biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis. BMC Neurol 18:90. https://doi.org/10.1186/s12883-018-1091-7
Huang J, Khademi M, Fugger L, Lindhe Ö, Novakova L, Axelsson M, Malmeström C, Constantinescu C, Lycke J, Piehl F, Olsson T, Kockum I (2020) Inflammation-related plasma and CSF biomarkers for multiple sclerosis. Proc Natl Acad Sci 117:12952–12960. https://doi.org/10.1073/pnas.1912839117
Stilund M, Gjelstrup MC, Petersen T, Møller HJ, Rasmussen PV, Christensen T (2015) Biomarkers of inflammation and axonal degeneration/damage in patients with newly diagnosed multiple sclerosis: contributions of the soluble CD163 CSF/serum ratio to a biomarker panel. PLoS One 10:e0119681. https://doi.org/10.1371/journal.pone.0119681
Santaella A, Kuiperij HB, van Rumund A, Esselink RAJ, van Gool AJ, Bloem BR, Verbeek MM (2020) Inflammation biomarker discovery in Parkinson’s disease and atypical parkinsonisms. BMC Neurol 20:26. https://doi.org/10.1186/s12883-020-1608-8
Hall S, Janelidze S, Surova Y, Widner H, Zetterberg H, Hansson O (2018) Cerebrospinal fluid concentrations of inflammatory markers in Parkinson’s disease and atypical parkinsonian disorders. Sci Rep 8:13276. https://doi.org/10.1038/s41598-018-31517-z
Morgan AR, Touchard S, Leckey C, O’Hagan C, Nevado-Holgado AJ, Barkhof F, Bertram L, Blin O, Bos I, Dobricic V, Engelborghs S, Frisoni G, Frölich L, Gabel S, Johannsen P, Kettunen P, Kłoszewska I, Legido-Quigley C, Lleó A, Martinez-Lage P, Mecocci P, Meersmans K, Molinuevo JL, Peyratout G, Popp J, Richardson J, Sala I, Scheltens P, Streffer J, Soininen H, Tainta-Cuezva M, Teunissen C, Tsolaki M, Vandenberghe R, Visser PJ, Vos S, Wahlund L-O, Wallin A, Westwood S, Zetterberg H, Lovestone S, Morgan BP (2019) Inflammatory biomarkers in Alzheimer’s disease plasma. Alzheimers Dement 15:776–787. https://doi.org/10.1016/j.jalz.2019.03.007
Huang L-K, Chao S-P, Hu C-J (2020) Clinical trials of new drugs for Alzheimer disease. J Biomed Sci 27:18. https://doi.org/10.1186/s12929-019-0609-7
Bard AJ, Faulkner LR (2001) In: Harris D, Swain E (eds) Electrochemical methods: fundamentals and applications, 2nd edn. Wiley, New York. ISBN: 978-0-471-04372-0
Grieshaber D, MacKenzie R, Vörös J, Reimhult E, Grieshaber D, MacKenzie R, Vörös J, Reimhult E (2008) Electrochemical biosensors—sensor principles and architectures. Sensors 8:1400–1458. https://doi.org/10.3390/s80314000
Randles JEB (1947) Kinetics of rapid electrode reactions. Faraday Discuss 1:11–19. https://doi.org/10.1039/DF9470100011
Cruz A, Queirós R, Abreu CM, Barata C, Fernandes R, Silva R, Ambrosio AF, Soares dos Reis R, Guimarães J, Sá MJ, Relvas JB, Freitas PP, Pinto IM (2019) Electrochemical immunosensor for TNFα-mediated inflammatory disease screening. ACS Chem Nerosci 10(6):2676–2682. https://doi.org/10.1021/acschemneuro.9b00036
Abreu CM, Thomas V, Knaggs P, Bunkheila A, Cruz A, Teixeira SR, Alpuim P, Francis LW, Gebril A, Ibrahim A, Margarit L, Gonzalez D, Freitas PP, Conlan RS, Mendes Pinto I (2020) Non-invasive molecular assessment of human embryo development and implantation potential. Biosens Bioelectron 157:112144. https://doi.org/10.1016/j.bios.2020.112144
Wink T, van Zuilen SJ, Bult A, van Bennekom WP (1997) Self-assembled monolayers for biosensors. Analyst 122:43R–50R. https://doi.org/10.1039/a606964i
Welch NG, Scoble JA, Muir BW, Pigram PJ (2017) Orientation and characterization of immobilized antibodies for improved immunoassays (review). Biointerphases 12:02D301. https://doi.org/10.1116/1.4978435
Hermanson GT (2013) In: Audet J, Preap M (eds) Bioconjugate techniques, 3rd edn. Elsevier, London. ISBN: 9780123822390
Denisin AK, Karns K, Herr AE (2012) Post-collection processing of Schirmer strip-collected human tear fluid impacts protein content. Analyst 137:5088. https://doi.org/10.1039/c2an35821b
Acknowledgments
I.M.P. and A.C. acknowledge the financial support from the Marie Curie COFUND Programme “NanoTRAINforGrowth,” from the European Union’s Seventh Framework Programme for research, technological development and demonstration under Grant Agreement No. 600375. This chapter is a result of the project advancing cancer research: from basic knowledge to application (NORTE-01-0145-FEDER-000029), cofinanced by Norte Portugal Regional Operational Programme (NORTE, 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund, European Union. This work was partially financed by N2020 project: RHAQ/COLAB NORTE-06-3559-FSE-000044 and FCT (Portuguese Foundation for Science and Technology).
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Cruz, A., Abreu, C.M., Freitas, P.P., Mendes Pinto, I. (2022). Impedimetric Immunosensing for Neuroinflammatory Biomarker Profiling. In: Peplow, P.V., Martinez, B., Gennarelli, T.A. (eds) Neurodegenerative Diseases Biomarkers. Neuromethods, vol 173. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1712-0_14
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DOI: https://doi.org/10.1007/978-1-0716-1712-0_14
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