CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2017; 75(09): 649-656
DOI: 10.1590/0004-282X20170110
VIEWS AND REVIEWS

Alzheimer’s disease and cytokine IL-10 gene polymorphisms: is there an association?

A doença de Alzheimer e os polimorfismos no gene da citocina IL-10: há alguma associação?
Carolina Antunes Magalhães
1   Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Análises Clínicas e Toxicológicas, Belo Horizonte MG, Brasil;
,
Maria das Graças Carvalho
1   Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Análises Clínicas e Toxicológicas, Belo Horizonte MG, Brasil;
,
Lirlândia Pires de Sousa
1   Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Análises Clínicas e Toxicológicas, Belo Horizonte MG, Brasil;
,
Paulo Caramelli
2   Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Clínica Médica, Belo Horizonte MG, Brasil.
,
Karina Braga Gomes
1   Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Análises Clínicas e Toxicológicas, Belo Horizonte MG, Brasil;
› Institutsangaben

ABSTRACT

Alzheimer’s disease (AD) is the most common form of dementia. In the last 15 years, a new theory has proposed the autoimmune mechanism as a trigger for AD. Studies on the association between AD and inflammatory biomarkers have yielded controversial results. Interleukin-10 (IL-10), an anti-inflammatory mediator, has been pointed out as one of the main cytokines associated with the occurrence of AD. Moreover, treatment that increases IL-10 levels could be a potential therapy for AD, since this cytokine acts on amyloid and pro-inflammatory molecule reduction. Based on the current literature, this study reviews evidence regarding the role of IL-10 polymorphisms in the context of AD, which has been shown to be of paramount importance for attenuating neuroinflammation, cognitive dysfunction and neurodegeneration.

RESUMO

A doença de Alzheimer (DA) é a forma mais comum de demência. Nos últimos 15 anos, uma nova teoria propõe um mecanismo autoimmune como o gatilho para a DA. Associações entre DA e biomarcadores inflamatórios têm sido registradas, contudo com resultados controversos. A interleucina-10 (IL-10), um mediador anti-inflamatório, tem sido apontada como uma das principais citocinas associadas com a ocorrência de DA. Além disso, os tratamentos que aumentam os níveis de IL-10 podem ser uma terapia potencial para DA, uma vez que esta citocina atua sobre a redução de substância amiloide e de moléculas pró-inflamatórias. Baseando-se em literaturas atuais, este estudo revisa evidências relacionadas com o papel da IL-10 e seus polimorfismos no contexto da DA, o qual se mostrou ser de fundamental importância para atenuar a neuroinflamação, a disfunção cognitiva e a neurodegeneração.

Support:

Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). LPS, MGC, PC and KBG are grateful to CNPq Research Fellowship (PQ).




Publikationsverlauf

Eingereicht: 09. Februar 2017

Angenommen: 13. Juni 2017

Artikel online veröffentlicht:
05. September 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Alzheimer’s Association. 2015 Alzheimer’s disease facts and figures. Alzheimers Dement. 2015;11(3):332-84. https://doi.org/10.1016/j.jalz.2015.02.003
  • 2 Heppner FL, Ransohoff RM, Becher B.Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci. 2015;16(6):358-72. https://doi.org/10.1038/nrn3880
  • 3 Nitrini R, Bottino CM, Albala C, Custodio Capuñay NS, Ketzoian C, Llibre Rodriguez JJ et al.Prevalence of dementia in Latin America: a collaborative study of population-based cohorts. Int Psychogeriatr. 2009;21(4):622-30. https://doi.org/10.1017/S1041610209009430
  • 4 Scassellati C, Zanardini R, Squitti R, Bocchio-Chiavetto L, Bonvicini C, Binetti G et al.Promoter haplotypes of interleukin-10 gene and sporadic Alzheimer’s disease. Neurosci Lett. 2004;356(2):119-22. https://doi.org/10.1016/j.neulet.2003.11.033
  • 5 Swardfager W, Lanctçt K, Rothenburg L, Wong A, Cappell J, Herrmann N. A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry. 2010;68(10):930-41. https://doi.org/10.1016/j.biopsych.2010.06.012
  • 6 Rosenberg RN, Lambracht-Washington D, Yu G, Xia W.Genomics of Alzheimer disease: a review. JAMA Neurol. 2016;73(7):867-74. https://doi.org/10.1001/jamaneurol.2016.0301
  • 7 Blach-Olszewska Z, Zaczynska E, Gustaw-Rothenberg K, Avila-Rodrigues M, Barreto GE, Leszek J et al.The innate immunity in Alzheimer disease- relevance to pathogenesis and therapy. Curr Pharm Des. 2015;21(25):3582-8. https://doi.org/10.2174/1381612821666150710144829
  • 8 Dubois RN. The Jeremiah Metzger Lecture: inflammation, immune modulators, and chronic disease. Trans Am Clin Climatol Assoc. 2015;126:230-6.
  • 9 Sardi F, Fassina L, Venturini L, Inguscio M, Guerriero F, Rolfo E et al.Alzheimer’s disease, autoimmunity and inflammation: the good, the bad and the ugly. Autoimmun Rev. 2011;11(2):149-53. https://doi.org/10.1016/j.autrev.2011.09.005
  • 10 Kiyota T, Ingraham KL, Swan RJ, Jacobsen MT, Andrews SJ, Ikezu T.AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice. Gene Ther. 2012;19(7):724-33. https://doi.org/10.1038/gt.2011.126
  • 11 Delaby C, Gabelle A, Blum D, Schraen-Maschke S, Moulinier A, Boulanghien J et al.Central Nervous System and Peripheral Inflammatory Processes in Alzheimer’s Disease: Biomarker Profiling Approach. Front Neurol 2015 Aug;6:181. https://doi.org/10.3389/fneur.2015.00181PMID:26379616
  • 12 Naert G, Rivest S. The role of microglial cell subsets in Alzheimer’s disease. Curr Alzheimer Res. 2011;8(2):151-5. https://doi.org/10.2174/156720511795256035
  • 13 Fuster-Matanzo A, Llorens-Martín M, Hernández F, Avila J.Role of neuroinflammation in adult neurogenesis and Alzheimer disease: therapeutic approaches. Mediators Inflamm. 2013;2013:260925. https://doi.org/10.1155/2013/260925
  • 14 Latta CH, Brothers HM, Wilcock DM. Neuroinflammation in Alzheimer’s disease: a source of heterogeneity and target for personalized therapy. Neuroscience. 2015;302:103-11. https://doi.org/10.1016/j.neuroscience.2014.09.061
  • 15 Steardo L Jr, Bronzuoli MR, Iacomino A, Esposito G, Steardo L, Scuderi C.Does neuroinflammation turn on the flame in Alzheimer’s disease? Focus on astrocytes. Front Neurosci. 2015;9:259. https://doi.org/10.3389/fnins.2015.00259
  • 16 Singhal G, Jaehne EJ, Corrigan F, Toben C, Baune BT.Inflammasomes in neuroinflammation and changes in brain function: a focused review. Front Neurosci. 2014;8:315. https://doi.org/10.3389/fnins.2014.00315
  • 17 Alam Q, Alam MZ, Mushtaq G, Damanhouri GA, Rasool M, Kamal MA et al.Inflammatory process in Alzheimer’s and Parkinson’s diseases: central role of cytokines. Curr Pharm Des. 2016;22(5):541-8. https://doi.org/10.2174/1381612822666151125000300
  • 18 Saleem M, Herrmann N, Swardfager W, Eisen R, Lanctçt KL.Inflammatory Markers in Mild Cognitive Impairment: A Meta-Analysis. J Alzheimers Dis. 2015;47(3):669-79. https://doi.org/10.3233/JAD-150042
  • 19 Verkhratsky A, Zorec R, Rodríguez JJ, Parpura V. Astroglia dynamics in ageing and Alzheimer’s disease. Curr Opin Pharmacol. 2016;26:74-9. https://doi.org/10.1016/j.coph.2015.09.011
  • 20 Julian A, Dugast E, Ragot S, Krolak-Salmon P, Berrut G, Dantoine T et al.There is no correlation between peripheral inflammation and cognitive status at diagnosis in Alzheimer’s disease. Aging Clin Exp Res. 2015;27(5):589-94. https://doi.org/10.1007/s40520-015-0332-5
  • 21 Sabat R.IL-10 family of cytokines. Cytokine Growth Factor Rev. 2010;21(5):315-24. https://doi.org/10.1016/j.cytogfr.2010.11.001
  • 22 Bagyinszky E, Youn YC, An SS, Kim SY.Characterization of inflammatory biomarkers and candidates for diagnosis of Alzheimer’s disease. Biochip J. 2014;8(3):155-62. https://doi.org/10.1007/s13206-014-8301-1
  • 23 Fiorentino DF, Bond MW, Mosmann TR.Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989;170(6):2081-95. https://doi.org/10.1084/jem.170.6.2081
  • 24 Acuner-Ozbabacan ES, Engin BH, Guven-Maiorov E, Kuzu G, Muratcioglu S, Baspinar A et al.The structural network of Interleukin-10 and its implications in inflammation and cancer. BMC Genomics. 2014;15 Suppl 4:S2. https://doi.org/10.1186/1471-2164-15-S4-S2
  • 25 Combarros O, Duijn CM, Hammond N, Belbin O, Arias-Vásquez A, Cortina-Borja M et al.Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer’s disease. J Neuroinflammation. 2009;6(1):22. https://doi.org/10.1186/1742-2094-6-22
  • 26 Ma SL, Tang NL, Lam LC, Chiu HF.The association between promoter polymorphism of the interleukin-10 gene and Alzheimer’s disease. Neurobiol Aging. 2005;26(7):1005-10. https://doi.org/10.1016/j.neurobiolaging.2004.08.010
  • 27 Rota E, Bellone G, Rocca P, Bergamasco B, Emanuelli G, Ferrero P. Increased intrathecal TGF-beta1, but not IL-12, IFN-gamma and IL-10 levels in Alzheimer’s disease patients. Neurol Sci. 2006;27(1):33-9. https://doi.org/10.1007/s10072-006-0562-6
  • 28 Richwine AF, Sparkman NL, Dilger RN, Buchanan JB, Johnson RW.Cognitive deficits in interleukin-10-deficient mice after peripheral injection of lipopolysaccharide. Brain Behav Immun. 2009;23(6):794-802. https://doi.org/10.1016/j.bbi.2009.02.020
  • 29 Henderson VW.Estrogen-containing hormone therapy and Alzheimer’s disease risk: understanding discrepant inferences from observational and experimental research. Neuroscience. 2006;138(3):1031-9. https://doi.org/10.1016/j.neuroscience.2005.06.017
  • 30 Ishunina TA, Fischer DF, Swaab DF. Estrogen receptor alpha and its splice variants in the hippocampus in aging and Alzheimer’s disease. Neurobiol Aging. 2007;28(11):1670-81. https://doi.org/10.1016/j.neurobiolaging.2006.07.024
  • 31 Luchetti S, Bossers K, Van de Bilt S, Agrapart V, Morales RR, Frajese GV et al.Neurosteroid biosynthetic pathways changes in prefrontal cortex in Alzheimer’s disease. Neurobiol Aging. 2011;32(11):1964-76. https://doi.org/10.1016/j.neurobiolaging.2009.12.014
  • 32 Cianciulli A, Dragone T, Calvello R, Porro C, Trotta T, Lofrumento DD et al.IL-10 plays a pivotal role in anti-inflammatory effects of resveratrol in activated microglia cells. Int Immunopharmacol. 2015;24(2):369-76. https://doi.org/10.1016/j.intimp.2014.12.035
  • 33 Guillot-Sestier MV, Doty KR, Gate D, Rodriguez J Jr, Leung BP, Rezai-Zadeh K et al.Il10 deficiency rebalances innate immunity to mitigate Alzheimer-like pathology. Neuron 2015;85(3):534-48. https://doi.org/10.1016/j.neuron.2014.12.068
  • 34 Chakrabarty P, Li A, Ceballos-Diaz C, Eddy JA, Funk CC, Moore B et al.IL-10 alters immunoproteostasis in APP mice, increasing plaque burden and worsening cognitive behavior. Neuron. 2015;85(3):519-33. https://doi.org/10.1016/j.neuron.2014.11.020
  • 35 Bryson KJ, Lynch MA.Linking T cells to Alzheimer’s disease: from neurodegeneration to neurorepair. Curr Opin Pharmacol. 2016;26:67-73. https://doi.org/10.1016/j.coph.2015.10.003
  • 36 Zheng C, Zhou XW, Wang JZ.The dual roles of cytokines in Alzheimer’s disease: update on interleukins, TNF-α, TGF-β and IFN-γ. Transl Neurodegener. 2016;5(1):7. https://doi.org/10.1186/s40035-016-0054-4
  • 37 Fraga VG, Guimarães HC, Lara VP, Teixeira AL, Barbosa MT, Carvalho MG et al.TGF-β1 Codon 10 T>C polymorphism influences short-term functional and cognitive decline in healthy oldest-old individuals: the Pietà study. J Alzheimers Dis. 2015;48(4):1077-81. https://doi.org/10.3233/JAD-150397
  • 38 Cousin E, Macé S, Rocher C, Dib C, Muzard G, Hannequin D et al.No replication of genetic association between candidate polymorphisms and Alzheimer’s disease. Neurobiol Aging. 2011;32(8):1443-51. https://doi.org/10.1016/j.neurobiolaging.2009.09.004
  • 39 Culpan D, Prince JA, Matthews S, Palmer L, Hughes A, Love S et al.Neither sequence variation in the IL-10 gene promoter nor presence of IL-10 protein in the cerebral cortex is associated with Alzheimer’s disease. Neurosci Lett. 2006;408(2):141-5. https://doi.org/10.1016/j.neulet.2006.08.068
  • 40 Depboylu C, Du Y, Müller U, Kurz A, Zimmer R, Riemenschneider M et al.Lack of association of interleukin-10 promoter region polymorphisms with Alzheimer’s disease. Neurosci Lett. 2003;342(1-2):132-4. https://doi.org/10.1016/S0304-3940(03)00231-3
  • 41 Lio D, Licastro F, Scola L, Chiappelli M, Grimaldi LM, Crivello A et al.Interleukin-10 promoter polymorphism in sporadic Alzheimer’s disease. Genes Immun. 2003;4(3):234-8. https://doi.org/10.1038/sj.gene.6363964
  • 42 Moraes CF, Benedet AL, Souza VC, Lins TC, Camargos EF, Naves JO et al.Cytokine gene polymorphisms and Alzheimer’s disease in Brazil. Neuroimmunomodulation. 2013;20(5):239-46. https://doi.org/10.1159/000350368
  • 43 Arosio B, Trabattoni D, Galimberti L, Bucciarelli P, Fasano F, Calabresi C et al.Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer’s disease. Neurobiol Aging. 2004;25(8):1009-15. https://doi.org/10.1016/j.neurobiolaging.2003.10.009
  • 44 Arosio B, Mastronardi L, Vergani C, Annoni G.Interleukin-10 promoter polymorphism in mild cognitive impairment and in its clinical evolution. Int J Alzheimers Dis. 2010;20:pii 854527. https://doi.org/10.4061/2010/854527.
  • 45 Bagnoli S, Cellini E, Tedde A, Nacmias B, Piacentini S, Bessi V et al.Association of IL10 promoter polymorphism in Italian Alzheimer’s disease. Neurosci Lett. 2007;418(3):262-5. https://doi.org/10.1016/j.neulet.2007.03.030
  • 46 Ma SL, Tang NL, Lam LC, Chiu HF.The association between promoter polymorphism of the interleukin-10 gene and Alzheimer’s disease. Neurobiol Aging. 2005;26(7):1005-10. https://doi.org/10.1016/j.neurobiolaging.2004.08.010
  • 47 Culpan D, Prince JA, Matthews S, Palmer L, Hughes A, Love S et al.Neither sequence variation in the IL-10 gene promoter nor presence of IL-10 protein in the cerebral cortex is associated with Alzheimer’s disease. Neurosci Lett. 2006;408(2):141-5. https://doi.org/10.1016/j.neulet.2006.08.068
  • 48 Ramos EM, Lin MT, Larson EB, Maezawa I, Tseng LH, Edwards KL et al. Tumor necrosis factor alpha and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease. Arch Neurol. 2006;63(8):1165-9. https://doi.org/10.1001/archneur.63.8.1165
  • 49 Vural P, Değirmencioğlu S, Parildar-Karpuzoğlu H, Doğru-Abbasoğlu S, Hanagasi HA, Karadağ B et al. The combinations of TNFalpha-308 and IL-6 -174 or IL-10 -1082 genes polymorphisms suggest an association with susceptibility to sporadic late-onset Alzheimer’s disease. Acta Neurol Scand. 2009;120(6):396-401. https://doi.org/10.1111/j.1600-0404.2009.01230.x
  • 50 Ribizzi G, Fiordoro S, Barocci S, Ferrari E, Megna M.Cytokine polymorphisms and Alzheimer disease: possible associations. Neurol Sci. 2010;31(3):321-5. https://doi.org/10.1007/s10072-010-0221-9
  • 51 Zhang Y, Zhang J, Tian C, Xiao Y, Li X, He C et al.The -1082G/A polymorphism in IL-10 gene is associated with risk of Alzheimer’s disease: a meta-analysis. J Neurol Sci 2011;303(1-2):133-8. https://doi.org/10.1016/j.jns.2010.12.005
  • 52 Di Bona D, Rizzo C, Bonaventura G, Candore G, Caruso C.Association between interleukin-10 polymorphisms and Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2012;29(4):751-9. https://doi.org/10.3233/JAD-2012-111838
  • 53 Kang HJ, Kim JM, Kim SW, Shin IS, Park SW, Kim YH et al.Associations of cytokine genes with Alzheimer’s disease and depression in an elderly Korean population. J Neurol Neurosurg Psychiatry. 2015;86(9):1002-7. https://doi.org/10.1136/jnnp-2014-308469
  • 54 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. https://doi.org/10.1016/j.imlet.2016.07.011
  • 55 Mun MJ, Kim JH, Choi JY, Jang WC.Genetic polymorphisms of interleukin genes and the risk of Alzheimer’s disease: an update meta-analysis. Meta Gene. 2016;8:1-10. https://doi.org/10.1016/j.mgene.2016.01.001
  • 56 Fraga VG, Guimarães HC, Teixeira AL, Barbosa MT, Carvalho MG, Caramelli P et al.Polymorphisms in cytokine genes influence cognitive and functional performance in a population aged 75 years and above. Int J Geriatr Psychiatry. 2016;2016. https://doi.org/10.1002/gps.4627