Neurodegenerative Diseases

Original Paper

Serum Interleukin-10 Levels Correlate with Cerebrospinal Fluid Amyloid Beta Deposition in Alzheimer Disease Patients

D'Anna L.a,b,f,g · Abu-Rumeileh S.a,b,d · Fabris M.c · Pistis C.c · Baldi A.e · Sanvilli N.a, b · Curcio F.c · Gigli G.L.a, b · D'Anna S.e · Valente M.a, b

Author affiliations

aDepartment of Experimental and Clinical Medical Sciences, University of Udine Medical School, bNeurology Clinic, Department of Neurosciences, Santa Maria della Misericordia University Hospital, and cInstitute of Clinical Pathology, Department of Laborator Medicine, University Hospital of Udine and University of Udine Medical School, Udine, dDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, and eStroke Unit and Neurology Ward, Neurology Department, San Tommaso dei Battuti Hospital, Venice, Italy; fDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, and g Department of Neurosciences, Imperial College London, London, UK

Keywords: CytokinesNeuroinflammationAlzheimer diseaseInterleukin-10Amyloid beta protein

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Neurodegener Dis 2017;17:227-234
https://doi.org/10.1159/000474940

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 31, 2016
Accepted: April 03, 2017
Published online: July 19, 2017
Issue release date: August 2017

Number of Print Pages: 8
Number of Figures: 2
Number of Tables: 4

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD

Abstract

Background and Objective: In Alzheimer disease (AD) inflammation becomes evident throughout the course of the disease. However, the association between inflammation, cognitive impairment, and cerebrospinal biomarkers (Aβ42, t-tau, p-tau181, and Aβ42/p-tau181 ratio) is poorly understood. Methods: A large panel of inflammatory cytokines (interleukin [IL]-1β, IL-1ra, IL-2, IL-4, IL-6, IL-10, IL-17, interferon-γ, tumor necrosis factor-α, and vascular endothelial growth factor) was analyzed using a multiplex immunoassay in 27 patients with a diagnosis of AD dementia and in 18 control subjects. In a subgroup with available cerebrospinal fluid (CSF) samples, cytokines in serum were correlated with the levels of neurodegenerative CSF biomarkers (Aβ42, t-tau, p-tau181, and Aβ42/p-tau181 ratio). Results: Compared to control subjects, AD patients showed a significant upregulation of IL-10, IL-1β, and IL-17 serum levels. Several cytokines appeared intercorrelated, and IL-10 in particular presented a significant inverse correlation with CFS levels of Aβ42 and the Aβ42/p-tau ratio. Conclusion: Our findings indicate that serum levels of IL-10 may represent a possible peripheral expression of amyloid beta deposition in AD patients.

© 2017 S. Karger AG, Basel



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References

  1. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carillo MC, Thies B, Weintraub S, Phelps CH: The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging and the Alzheimer's Association workgroup. Alzheimers Dement 2011;7:263-269.
    External Resources
  2. Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L: Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 2006;5:228-234.
    External Resources
  3. Fagan AM, Head D, Shah AR, Marcus D, Mintun M, Morris JC, Holtzman DM: Decreased cerebrospinal fluid Aβ42 correlates with brain atrophy in cognitively normal elderly. Ann Neurol 2009;65:176-183.
    External Resources
  4. Blennow K, Hampel H: CSF markers for incipient Alzheimer's disease. Lancet Neurol 2003;2:605-613.
    External Resources
  5. Henriksen K, O'Bryant SE, Hampel H, Trojanowski JQ, Montine TJ, Jeromin A, Blennow K, Lönneborg A, Wyss-Coray T, Soares H, Bazenet C, Sjögren M, Hu W, Lovestone S, Karsdal MA, Weiner MW, et al: The future of blood-based biomarkers for Alzheimer's disease. Alzheimers Dement 2014;10:115-131.
    External Resources
  6. Ray S, Britschgi M, Herbert C, Takeda-Uchimura Y, Boxer A, Blennow K, Friedman LF, Galasko DR, Jutel M, Karydas A, Kaye JA, Leszek J, Miller BL, Minthon L, Quinn JF, Rabinovici GD, Robinson WH, Sabbagh MN, So YT, Sparks DL, Tabaton M, Tinklenberg J, Yesavage JA, Tibshirani R, Wyss-Coray T: Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nat Med 2007;13:1359-1362.
    External Resources
  7. Marksteiner J, Kemmler G, Weiss EM, Knaus G, Ullrich C, Mechtcheriakov S, Oberbauer H, Auffinger S, Hinterhölzl J, Hinterhuber H, Humpel C: Five out of 16 plasma signaling proteins are enhanced in plasma of patients with mild cognitive impairment and Alzheimer's disease. Neurobiol Aging 2011;32:539-540.
    External Resources
  8. Soares HD, Potter WZ, Pickering E, Kuhn M, Immermann FW, Shera DM, Ferm M, Dean RA, Simon AJ, Swenson F, Siuciak JA, Kaplow J, Thambisetty M, Zagouras P, Koroshetz WJ, Wan HI, Trojanowski JQ, Shaw LM; Biomarkers Consortium Alzheimer's Disease Plasma Proteomics Project: Plasma biomarkers associated with the apolipoprotein E genotype and Alzheimer disease. Arch Neurol 2012;69:1310-1317.
    External Resources
  9. Doecke JD, Laws SM, Faux NG, Wilson W, Burnham SC, Lam C-P, Mondal A, Bedo J, Bush AI, Brown B, De Ruyck K, Ellis KA, Fowler C, Gupta VB, Head R, Macaulay SL, Pertile K, Rowe CC, Rembach A, Rodrigues M, Rumble R, Szoeke C, Taddei K, Taddei T, Trounson B, Ames D, Masters CL, Martins RN; Alzheimer's Disease Neuroimaging Initiative; Australian Imaging Biomarker and Lifestyle Research Group: Blood-based protein biomarkers for diagnosis of Alzheimer disease. Arch Neurol 2012;69:1318-1325.
    External Resources
  10. O'Bryant SE, Xiao G, Barber R, Reisch J, Doody R, Fairchild T, Adams P, Waring S, Diaz-Arrastia R; Texas Alzheimer's Research Consortium: A serum protein-based algorithm for the detection of Alzheimer disease. Arch Neurol 2010;67:1077-1081.
    External Resources
  11. Tuppo EE, Arias HR: The role of inflammation in Alzheimer's disease. Int J Biochem Cell Biol 2005;37:289-305.
    External Resources
  12. Heneka MT, Carson MJ, Khoury El J, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, Petzold GC, Town T, Morgan D, Shinohara ML, Perry VH, Holmes C, Bazan NG, Brooks DJ, Hunot S, Joseph B, Deigendesch N, et al: Neuroinflammation in Alzheimer's disease. Lancet Neurol 2015;14:388-405.
    External Resources
  13. Patel NS, Paris D, Mathura V, Quadros AN, Crawford FC, Mullan MJ: Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease. J Neuroinflammation 2005;2:9.
    External Resources
  14. Lio D, Licastro F, Scola L, Chiappelli M, Grimaldi LM, Crivello A, Colonna-Romano G, Candore G, Franceschi C, Caruso C: Interleukin-10 promoter polymorphism in sporadic Alzheimer's disease. Genes Immun 2003;4:234-238.
    External Resources
  15. Chakrabarty P, Li A, Ceballos-Diaz C, Eddy JA, Funk CC, Moore B, DiNunno N, Rosario AM, Cruz PE, Verbeeck C, Sacino A, Nix S, Janus C, Price ND, Das P, Golde TE: IL-10 alters immunoproteostasis in APP mice, increasing plaque burden and worsening cognitive behavior. Neuron 2015;85:519-533.
    External Resources
  16. Li X, Long J, He T, Belshaw R, Scott J: Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer's disease. Sci Rep 2015;5:12393.
    External Resources
  17. Zhang B, Gaiteri C, Bodea LG, Wang Z, McElwee J, Podtelezhnikov AA, Zhang C, Xie T, Tran L, Dobrin R, Fluder E, Clurman B, Melquist S, Narayanan M, Suver C, Shah H, Mahajan M, Gillis T, Mysore J, MacDonald ME, Lamb JR, Bennett DA, Molony C, Stone DJ, Gudnason V, Myers AJ, Schadt EE, Neumann H, Zhu J, Emilsson V: Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease. Cell 2013;153:707-720.
    External Resources
  18. Guillot-Sestier M-V, Doty KR, Gate D, Rodriguez J Jr, Leung BP, Rezai-Zadeh K, Town T: IL10 deficiency rebalances innate immunity to mitigate Alzheimer-like pathology. Neuron 2015;85:534-548.
    External Resources
  19. Angelopoulos P, Agouridaki H, Vaiopoulos H, Siskou E, Doutsou K, Costa V, Baloyiannis SI: Cytokines in Alzheimer's disease and vascular dementia. Int J Neurosci 2008;118:1659-1672.
    External Resources
  20. Loewenbrueck KF, Tigno-Aranjuez JT, Boehm BO, Lehmann PV, Tary-Lehmann M: Th1 responses to beta-amyloid in young humans convert to regulatory IL-10 responses in Down syndrome and Alzheimer's disease. Neurobiol Aging 2010;31:1732-1742.
    External Resources
  21. Leung R, Proitsi P, Simmons A, Lunnon K, Güntert A, Kronenberg D, Pritchard M, Tsolaki M, Mecocci P, Kloszewska I, Vellas B, Soininen H, Wahlund L-O, Lovestone S: Inflammatory proteins in plasma are associated with severity of Alzheimer's disease. PLoS One 2013;8:e64971.
    External Resources
  22. Guillot-Sestier M-V, Doty KR, Town T: Innate immunity fights Alzheimer's disease. Trends Neurosci 2015;38:674-681.
    External Resources
  23. Vargas-Alarcón G, Juárez-Cedillo E, Martínez-Rodríguez N, Fragoso JM, García-Hernández N, Juárez-Cedillo T: Association of interleukin-10 polymorphisms with risk factors of Alzheimer's disease and other dementias (SADEM study). Immunol Lett 2016;177:47-52.
    External Resources
  24. Szczepanik AM, Funes S, Petko W, Ringheim GE: IL-4, IL-10 and IL-13 modulate Aβ1-42-induced cytokine and chemokine production in primary murine microglia and a human monocyte cell line. J Neuroimmunol 2001;113:49-62.
    External Resources
  25. Torres KC, Araújo Pereira P, Lima GS, Bozzi IC, Rezende VB, Bicalho MA, Moraes EN, Miranda DM, Romano-Silva MA: Increased frequency of T cells expressing IL-10 in Alzheimer disease but not in late-onset depression patients. Prog Neuropsychopharmacol Biol Psychiatry 2013;47:40-45.
    External Resources
  26. Banchereau J, Pascual V, O'Garra A: From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines. Nat Immunol 2012;13:925-931.
    External Resources
  27. Michaud J-P, Rivest S: Anti-inflammatory signaling in microglia exacerbates Alzheimer's disease-related pathology. Neuron 2015;85:450-452.
    External Resources
  28. Shaftel SS, Griffin WST, O'Banion MK: The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective. J Neuroinflammation 2008;5:7.
    External Resources
  29. Winter CD, Iannotti F, Pringle AK, Trikkas C, Clough GF, Church MK: A microdialysis method for the recovery of IL-1β, IL-6 and nerve growth factor from human brain in vivo. J Neurosci Methods 2002;119:45-50.
    External Resources
  30. 30 Zuliani G, Ranzini M, Guerra G, Rossi L, Munari MR, Zurlo A, Volpato S, Atti AR, Blè A, Fellin R: Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia. J Psychiatr Res 2007;41:686-693.
    External Resources
  31. De Luigi A, Pizzimenti S, Quadri P, Lucca U, Tettamanti M, Fragiacomo C, De Simoni MG: Peripheral inflammatory response in Alzheimer's disease and multiinfarct dementia. Neurobiol Dis 2002;11:308-314.
    External Resources
  32. Yasutake C, Kuroda K, Yanagawa T, Okamura T, Yoneda H: Serum BDNF, TNF-α and IL-1β levels in dementia patients: comparison between Alzheimer's disease and vascular dementia. Eur Arch Psychiatry Clin Neurosci 2006;256:402-406.
    External Resources
  33. Licastro F, Pedrini S, Caputo L, Annoni G, Davis LJ, Ferri C, Casadei V, Grimaldi LM: Increased plasma levels of interleukin-1, interleukin-6 and α-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain? J Neuroimmunol 2000;103:97-102.
    External Resources
  34. Khemka VK, Ganguly A, Bagchi D, Ghosh A, Bir A, Biswas A, Chattopadhyay S, Chakrabarti S: Raised serum proinflammatory cytokines in Alzheimer's disease with depression. Aging Dis 2014;5:170-176.
    External Resources
  35. Hickman SE, Allison EK, Khoury El J: Microglial dysfunction and defective β-amyloid clearance pathways in aging Alzheimer's disease mice. J Neurosci 2008;28:8354-8360.
    External Resources
  36. Song C, Zhang Y, Dong Y: Acute and subacute IL-1β administrations differentially modulate neuroimmune and neurotrophic systems: possible implications for neuroprotection and neurodegeneration. J Neuroinflammation 2013;10:59.
    External Resources
  37. Liu L, Aboud O, Jones RA, Mrak RE, Griffin WST, Barger SW: Apolipoprotein E expression is elevated by interleukin 1 and other interleukin 1-induced factors. J Neuroinflammation 2011;8:175.
    External Resources
  38. Chen J-M, Jiang G-X, Li Q-W, Zhou Z-M, Cheng Q: Increased serum levels of interleukin-18, -23 and -17 in Chinese patients with Alzheimer's disease. Dement Geriatr Cogn Disord 2014;38:321-329.
    External Resources
  39. Behairi N, Belkhelfa M, Mesbah-Amroun H, Rafa H, Belarbi S, Tazir M, et al: All-trans-retinoic acid modulates nitric oxide and interleukin-17A production by peripheral blood mononuclear cells from patients with Alzheimer's disease. Neuroimmunomodulation 2015;22:385-393.
    External Resources
  40. Zhang J, Ke K-F, Liu Z, Qiu Y-H, Peng Y-P: Th17 cell-mediated neuroinflammation is involved in neurodegeneration of Aβ1-42-induced Alzheimer's disease model rats. PLoS One 2013;8:e75786.
    External Resources
  41. Sun J, Zhang S, Zhang X, Zhang X, Dong H, Qian Y: IL-17A is implicated in lipopolysaccharide-induced neuroinflammation and cognitive impairment in aged rats via microglial activation. J Neuroinflammation 2015;12:165.
    External Resources
  42. Belkhelfa M, Rafa H, Medjeber O, Arroul-Lammali A, Behairi N, Abada-Bendib M, Makrelouf M, Belarbi S, Masmoudi AN, Tazir M, Touil-Boukoffa C: IFN-γ and TNF-α are involved during Alzheimer disease progression and correlate with nitric oxide production: a study in Algerian patients. J Interferon Cytokine Res 2014;34:839-847.
    External Resources
  43. 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: CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Lancet Neurol 2016;15:673-684.
    External Resources
  44. O'Bryant SE, Mielke MM, Rissman RA, Lista S, Vanderstichele H, Zetterberg H, Lewczuk P, Posner H, Hall J, Johnson L, Fong YL, Luthman J, Jeromin A, Batrla-Utermann R, Villarreal A, Britton G, Snyder PJ, Henriksen K, Grammas P, Gupta V, Martins R, Hampel H; Biofluid Based Biomarker Professional Interest Area: Blood-based biomarkers in Alzheimer disease: current state of the science and a novel collaborative paradigm for advancing from discovery to clinic. Alzheimers Dement 2017;13:45-58.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 31, 2016
Accepted: April 03, 2017
Published online: July 19, 2017
Issue release date: August 2017

Number of Print Pages: 8
Number of Figures: 2
Number of Tables: 4

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD

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2017, Vol.17, No. 4-5

August 2017

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Sebastiano D'Anna and Mariarosaria Valente are equally last authors of this paper.
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