Generic placeholder image

Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

The Association between TNF-alpha, IL-1 alpha and IL-10 with Alzheimer's Disease

Author(s): Marija Culjak, Matea N. Perkovic, Suzana Uzun, Dubravka S. Strac, Gordana N. Erjavec, Mirjana B. Leko, Goran Simic, Lucija Tudor, Marcela Konjevod, Oliver Kozumplik, Ninoslav Mimica and Nela Pivac*

Volume 17, Issue 11, 2020

Page: [972 - 984] Pages: 13

DOI: 10.2174/1567205017666201130092427

Price: $65


Background: Sporadic Alzheimer’s Disease (AD) is assumed to be associated with different biological/genetic vulnerability, as well as with neuroinflammation, mediated by cytokines. The present study evaluated the role of cytokines in AD.

Objective: The aim was to determine the possible association of TNF-α (rs1800629), IL1-α (rs1800587) and IL-10 (rs1800896) polymorphisms with AD, and to assess serum TNF-α, IL-1α and IL-10 concentrations in patients with AD and in subjects with mild cognitive impairment (MCI).

Methods: The study included 645 Caucasian participants: 395 subjects with AD and 250 subjects with MCI. Genotyping was performed using real-time PCR in all 645 subjects, while serum concentrations of TNF-α, IL-1α and IL-10 and were determined using ELISA in 174 subjects.

Results: The frequency of the TNF-α rs1800629, IL1-α rs1800587 or IL-10 rs1800896 genotypes did not differ significantly between patients with AD and MCI. Serum concentration of IL-1α and IL-10 were significantly decreased, while the concentration of TNF-α was significantly higher in patients with AD than in MCI subjects. TNF-α, IL1-α or IL-10 concentrations were similar in subjects with AD or MCI subdivided into carriers of the corresponding TNF-α rs1800629, IL1-α rs1800587 or IL-10 rs1800896 genotypes.

Conclusion: Similar distribution of the IL1-α rs1800587, TNF-α rs1800629 or IL-10 rs1800896 genotypes in subjects with AD and MCI failed to confirm that these specific risk genotypes are associated with vulnerability to develop AD. Alteration in IL-1α, IL-10 and TNF-α concentrations in patients with AD partially confirmed the association with the neuroinflammatory response in AD.

Keywords: Alzheimer's disease, mild cognitive impairment, TNF-α rs1800629, IL1-α rs1800587, IL-10 rs1800896, IL-1α, IL-10, TNF-α.

« Previous
Perl DP. Neuropathology of Alzheimer’s disease. Mt Sinai J Med 2010; 77(1): 32-42.
[] [PMID: 20101720]
Castellani RJ, Rolston RK, Smith MA. Alzheimer disease. Dis Mon 2010; 56(9): 484-546.
[] [PMID: 20831921]
Zucchella C, Sinforiani E, Tamburin S, et al. The multidisciplinary approach to Alzheimer’s disease and Dementia. A narrative review of non-pharmacological treatment. Front Neurol 2018; 9: 1058.
[] [PMID: 30619031]
Murman DL. The impact of age on cognition. Semin Hear 2015; 36(3): 111-21.
[] [PMID: 27516712]
Geda YE. Mild cognitive impairment in older adults. Curr Psychiatry Rep 2012; 14(4): 320-7.
[] [PMID: 22773365]
Campbell NL, Unverzagt F, LaMantia MA, Khan BA, Boustani MA. Risk factors for the progression of mild cognitive impairment to dementia. Clin Geriatr Med 2013; 29(4): 873-93.
[] [PMID: 24094301]
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999; 56(3): 303-8.
[] [PMID: 10190820]
Mantzavinos V, Alexiou A. Biomarkers for Alzheimer’s disease diagnosis. Curr Alzheimer Res 2017; 14(11): 1149-54.
[] [PMID: 28164766]
Meraz-Ríos MA, Toral-Rios D, Franco-Bocanegra D, Villeda-Hernández J, Campos-Peña V. Inflammatory process in Alzheimer’s Disease. Front Integr Nuerosci 2013; 7: 59.
[] [PMID: 23964211]
Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell 2010; 140(6): 918-34.
[] [PMID: 20303880]
Combarros O, Sánchez-Juan P, Riancho JA, et al. Aromatase and interleukin-10 genetic variants interactively modulate Alzheimer’s disease risk. J Neural Transm (Vienna) 2008; 115(6): 863-7.
[] [PMID: 18299793]
Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell 2014; 157(1): 121-41.
[] [PMID: 24679531]
Cameron MJ, Kelvin DJ. Cytokines, chemokines and their receptors Madame Curie Bioscience Database 2000-13 [Internet]
Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin 2007; 45(2): 27-37.
[] [PMID: 17426506]
Arango Duque G, Descoteaux A. Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol 2014; 5: 491.
[] [PMID: 25339958]
Vitkovic L, Maeda S, Sternberg E. Anti-inflammatory cytokines: expression and action in the brain. Neuroimmunomodulation 2001; 9(6): 295-312.
[] [PMID: 12045357]
Chen WW, Zhang X, Huang WJ. Role of neuroinflammation in neurodegenerative diseases. (Review) Mol Med Rep 2016; 13(4): 3391-6.
[] [PMID: 26935478]
García Morán GA, Parra-Medina R, Cardona AG, Quintero-Ronderos P, Rodríguez EG. Cytokines, chemokines and growth factors Autoimmunity: from bench to bedside. Bogota, Colombia: El Rosario University Press 2013. [Internet
Chen L, Deng H, Cui H, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 2017; 9(6): 7204-18.
[] [PMID: 29467962]
Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest 2000; 117(4): 1162-72.
[] [PMID: 10767254]
Cavaillon JM. Pro- versus anti-inflammatory cytokines: myth or reality. Cell Mol Biol 2001; 47(4): 695-702.
[PMID: 11502077]
Brosseron F, Krauthausen M, Kummer M, Heneka MT. Body fluid cytokine levels in mild cognitive impairment and Alzheimer’s disease: a comparative overview. Mol Neurobiol 2014; 50(2): 534-44.
[] [PMID: 24567119]
Fillit H, Ding WH, Buee L, et al. Elevated circulating tumor necrosis factor levels in Alzheimer’s disease. Neurosci Lett 1991; 129(2): 318-20.
[] [PMID: 1745413]
Tarkowski E, Andreasen N, Tarkowski A, Blennow K. Intrathecal inflammation precedes development of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2003; 74(9): 1200-5. [a
[ ] [PMID: 12933918]
Cheng X, Shen Y, Li R. Targeting TNF: a therapeutic strategy for Alzheimer’s disease. Drug Discov Today 2014; 19(11): 1822-7.
[] [PMID: 24998784]
Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med 2015; 3(10): 136.
[PMID: 26207229]
Decourt B, Lahiri DK, Sabbagh MN. Targeting tumor necrosis factor alpha for Alzheimer’s disease. Curr Alzheimer Res 2017; 14(4): 412-25.
[PMID: 27697064]
Alvarez A, Cacabelos R, Sanpedro C, García-Fantini M, Aleixandre M. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging 2007; 28(4): 533-6.
[] [PMID: 16569464]
Tarkowski E, Liljeroth AM, Minthon L, Tarkowski A, Wallin A, Blennow K. Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull 2003; 61(3): 255-60.
[] [PMID: 12909295]
Yamamoto M, Kiyota T, Horiba M, et al. Interferon-gamma and tumor necrosis factor-alpha regulate amyloid-beta plaque deposition and beta-secretase expression in Swedish mutant APP transgenic mice. Am J Pathol 2007; 170(2): 680-92.
[] [PMID: 17255335]
Liao YF, Wang BJ, Cheng HT, Kuo LH, Wolfe MS. Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J Biol Chem 2004; 279(47): 49523-32.
[] [PMID: 15347683]
Hickman SE, Allison EK, El Khoury J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J Neurosci 2008; 28(33): 8354-60.
[] [PMID: 18701698]
Lourenco MV, Clarke JR, Frozza RL, et al. TNF-α mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer’s β-amyloid oligomers in mice and monkeys. Cell Metab 2013; 18(6): 831-43.
[] [PMID: 24315369]
Janelsins MC, Mastrangelo MA, Park KM, et al. Chronic neuron-specific tumor necrosis factor-alpha expression enhances the local inflammatory environment ultimately leading to neuronal death in 3xTg-AD mice. Am J Pathol 2008; 173(6): 1768-82.
[] [PMID: 18974297]
McGeer EG, McGeer PL. Inflammatory processes in Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27(5): 741-9.
[] [PMID: 12921904]
Di Bona D, Candore G, Franceschi C, et al. Systematic review by meta-analyses on the possible role of TNF-alpha polymorphisms in association with Alzheimer’s disease. Brain Res Brain Res Rev 2009; 61(2): 60-8.
[] [PMID: 19445962]
Tarkowski E, Liljeroth AM, Nilsson A, et al. TNF gene polymorphism and its relation to intracerebral production of TNFalpha and TNFbeta in AD. Neurology 2000; 54(11): 2077-81.
[] [PMID: 10851366]
Wilson AG, di Giovine FS, Duff GW. Genetics of tumour necrosis factor-alpha in autoimmune, infectious, and neoplastic diseases. J Inflamm 1995; 45(1): 1-12.
[PMID: 7583349]
Ardebili SM, Yeghaneh T, Gharesouran J, et al. Genetic association of TNF-α-308 G/A and -863 C/A polymorphisms with late onset Alzheimer’s disease in Azeri Turk population of Iran. J Res Med Sci 2011; 16(8): 1006-13.
[PMID: 22279475]
Laws SM, Perneczky R, Wagenpfeil S, et al. TNF polymorphisms in Alzheimer disease and functional implications on CSF beta-amyloid levels. Hum Mutat 2005; 26(1): 29-35.
[] [PMID: 15895461]
Manoochehri M, Kamali K, Rahgozar M, Ohadi M, Farrokhi H, Khorshid HR. Lack of association between tumor necrosis factor-alpha -308 g/a polymorphism and risk of developing late-onset Alzheimer’s disease in an Iranian population. Avicenna J Med Biotechnol 2009; 1(3): 193-7.
[PMID: 23408162]
Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011; 117(14): 3720-32.
[] [PMID: 21304099]
Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev 2018; 281(1): 8-27.
[] [PMID: 29247995]
Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: back to the future. Immunity 2013; 39(6): 1003-18.
[] [PMID: 24332029]
Shaftel SS, Griffin WS, O’Banion MK. The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective. J Neuroinflammation 2008; 5: 7.
[] [PMID: 18302763]
Malik A, Kanneganti TD. Function and regulation of IL-1α in inflammatory diseases and cancer. Immunol Rev 2018; 281(1): 124-37.
[] [PMID: 29247991]
Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 2009; 27: 519-50.
[] [PMID: 19302047]
Mrak RE, Griffin WS. Interleukin-1 and the immunogenetics of Alzheimer disease. J Neuropathol Exp Neurol 2000; 59(6): 471-6.
[] [PMID: 10850859]
Sheng JG, Jones RA, Zhou XQ, et al. Interleukin-1 promotion of MAPK-p38 overexpression in experimental animals and in Alzheimer’s disease: potential significance for tau protein phosphorylation. Neurochem Int 2001; 39(5-6): 341-8.
[] [PMID: 11578769]
Griffin WS, Sheng JG, Roberts GW, Mrak RE. Interleukin-1 expression in different plaque types in Alzheimer’s disease: significance in plaque evolution. J Neuropathol Exp Neurol 1995; 54(2): 276-81.
[] [PMID: 7876895]
Buxbaum JD, Oishi M, Chen HI, et al. Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein precursor. Proc Natl Acad Sci USA 1992; 89(21): 10075-8.
[] [PMID: 1359534]
Italiani P, Puxeddu I, Napoletano S, et al. Circulating levels of IL-1 family cytokines and receptors in Alzheimer’s disease: new markers of disease progression? J Neuroinflammation 2018; 15(1): 342.
[] [PMID: 30541566]
Griffin WS, Nicoll JA, Grimaldi LM, Sheng JG, Mrak RE. The pervasiveness of interleukin-1 in alzheimer pathogenesis: a role for specific polymorphisms in disease risk. Exp Gerontol 2000; 35(4): 481-7.
[] [PMID: 10959036]
Rainero I, Bo M, Ferrero M, Valfrè W, Vaula G, Pinessi L. Association between the interleukin-1alpha gene and Alzheimer’s disease: a meta-analysis. Neurobiol Aging 2004; 25(10): 1293-8.
[] [PMID: 15465625]
Qin X, Peng Q, Zeng Z, et al. Interleukin-1A -889C/T polymorphism and risk of Alzheimer’s disease: a meta-analysis based on 32 case-control studies. J Neurol 2012; 259(8): 1519-29.
[] [PMID: 22234841]
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.
[] [PMID: 27014584]
Iyer SS, Cheng G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol 2012; 32(1): 23-63.
[] [PMID: 22428854]
Sabat R. IL-10 family of cytokines. Cytokine Growth Factor Rev 2010; 21(5): 315-24.
[] [PMID: 21112807]
Acuner-Ozbabacan ES, Engin BH, Guven-Maiorov E, et al. The structural network of Interleukin-10 and its implications in inflammation and cancer. BMC Genomics 2014; 15(4): S2.
[] [PMID: 25056661]
Lobo-Silva D, Carriche GM, Castro AG, Roque S, Saraiva M. Balancing the immune response in the brain: IL-10 and its regulation. J Neuroinflammation 2016; 13(1): 297.
[] [PMID: 27881137]
Bagyinszky E, Youn YC, An SS, Kim SY. Characterization of inflammatory biomarkers and candidates for diagnosis of Alzheimer’s disease Biochip J 2014; 8: 155-62..
D’Anna L, Abu-Rumeileh S, Fabris M, et al. Serum interleukin-10 levels correlate with cerebrospinal fluid amyloid beta deposition in Alzheimer disease patients. Neurodegener Dis 2017; 17(4-5): 227-34.
[] [PMID: 28719891]
Pedrini S, Gupta VB, Hone E, et al. AIBL Research Group. A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort. Sci Rep 2017; 7(1): 14057.
[] [PMID: 29070909]
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.
[] [PMID: 16688597]
Magalhães CA, Carvalho MDG, Sousa LP, Caramelli P, Gomes KB. Alzheimer’s disease and cytokine IL-10 gene polymorphisms: is there an association? Arq Neuropsiquiatr 2017; 75(9): 649-56.
[] [PMID: 28977146]
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.
[] [PMID: 22356904]
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.
[] [PMID: 27474414]
Little J, Higgins JPT, Ioannidis JPA, et al. Strengthening the reporting of genetic association studies (STREGA)- an extension of the STROBE statement. Genet Epidemiol 2009; 33(7): 581-98.
[] [PMID: 19278015]
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 263-9.
[] [PMID: 21514250]
Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 270-9.
[] [PMID: 21514249]
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013; 310(20): 2191-4.
[] [PMID: 24141714]
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16(3): 1215.
[] [PMID: 3344216]
Chiswick EL, Duffy E, Japp B, Remick D. Detection and quantification of cytokines and other biomarkers. Methods Mol Biol 2012; 844: 15-30.
[] [PMID: 22262432]
Ghasemi A, Zahediasl S. Normality tests for statistical analysis: a guide for non-statisticians. Int J Endocrinol Metab 2012; 10(2): 486-9.
[] [PMID: 23843808]
Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 2009; 41(4): 1149-60.
[] [PMID: 19897823]
Su F, Bai F, Zhang Z. Inflammatory cytokines and Alzheimer’s disease: a review from the perspective of genetic polymorphisms. Neurosci Bull 2016; 32(5): 469-80.
[] [PMID: 27568024]
Griffin WS, Mrak RE. Interleukin-1 in the genesis and progression of and risk for development of neuronal degeneration in Alzheimer’s disease. J Leukoc Biol 2002; 72(2): 233-8.
[PMID: 12149413]
Dominici R, Cattaneo M, Malferrari G, et al. Cloning and functional analysis of the allelic polymorphism in the transcription regulatory region of interleukin-1 alpha. Immunogenetics 2002; 54(2): 82-6.
[] [PMID: 12037600]
Wei X, Chen X, Fontanilla C, et al. C/T conversion alters interleukin-1A promoter function in a human astrocyte cell line. Life Sci 2007; 80(12): 1152-6.
[] [PMID: 17257626]
Combarros O, Sánchez-Guerra M, Infante J, Llorca J, Berciano J. Gene dose-dependent association of interleukin-1A [-889] allele 2 polymorphism with Alzheimer’s disease. J Neurol 2002; 249(9): 1242-5.
[] [PMID: 12242547]
Combarros O, Llorca J, Sánchez-Guerra M, Infante J, Berciano J. Age-dependent association between interleukin-1A (-889) genetic polymorphism and sporadic Alzheimer’s disease. A meta-analysis. J Neurol 2003; 250(8): 987-9.
[] [PMID: 12928921]
Hua Y, Zhao H, Kong Y, Lu X. Meta-analysis of the association between the interleukin-1A -889C/T polymorphism and Alzheimer’s disease. J Neurosci Res 2012; 90(9): 1681-92.
[] [PMID: 22513697]
Zhang Q, Yao Z, Xu L, Cheng X, Cui T. Association of IL-1α, IL-1β, IL-18 and IL-33 genetic variants with the risk of Alzheimer disease in a Chinese population. Int J Clin Exp Pathol 2017; 10: 2127-34.
Hayes A, Green EK, Pritchard A, et al. A polymorphic variation in the interleukin 1A gene increases brain microglial cell activity in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2004; 75(10): 1475-7.
[] [PMID: 15377701]
Babic Leko M, Nikolac Perkovic M, Klepac N, et al. IL-1β, IL-6, IL-10, and TNFα single nucleotide polymorphisms in human influence the susceptibility to AD pathology. J Alzheimers Dis 2020; 75(3): 1029-47.
Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 2007; 39(1): 17-23.
[] [PMID: 17192785]
Serretti A, Olgiati P, Politis A, et al. Lack of association between interleukin-1 alpha rs1800587 polymorphism and Alzheimer’s disease in two Independent European samples. J Alzheimers Dis 2009; 16(1): 181-7.
[] [PMID: 19158434]
Yildiz SH, Erdogan MO, Artan S, et al. Association of Alzheimer’s disease with APOE and IL-1α gene polymorphisms. Am J Alzheimers Dis Other Demen 2015; 30(8): 756-61.
[] [PMID: 23038715]
Ter Horst R, Jaeger M, Smeekens SP, et al. Host and environmental factors influencing individual human cytokine responses. Cell 2016; 167(4): 1111-1124.e13.
[] [PMID: 27814508]
Ng A, Tam WW, Zhang MW, et al. Ho IL-1β, IL-6, TNF- α and CRP in elderly patients with depression or Alzheimer’s disease: Systematic review and meta-analysis. Sci Rep 2018; 8(1): 12050.
[] [PMID: 30104698]
Griffin WS, Sheng JG, Royston MC, et al. Glial-neuronal interactions in Alzheimer’s disease: the potential role of a ‘cytokine cycle’ in disease progression. Brain Pathol 1998; 8(1): 65-72.
[] [PMID: 9458167]
Li Y, Liu L, Barger SW, Griffin WS. Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway. J Neurosci 2003; 23(5): 1605-11.
[] [PMID: 12629164]
Hamdan AA, Melconian AK, Ali A, Alhaidary AF. The level of IL-1α, IL-10 and IL-17A in Alzheimer’s disease patients: comparative study. Baghdad Sci J 2014; 11: 1486-92..
Kim J-W, Stewart R, Kang H-J, et al. Longitudinal associations between serum cytokine levels and dementia. Front Psychiatry 2018; 9: 606.
[] [PMID: 30510525]
Kawaguchi Y, Tochimoto A, Hara M, et al. Contribution of single nucleotide polymorphisms of the IL1A gene to the cleavage of precursor IL-1alpha and its transcription activity. Immunogenetics 2007; 59(6): 441-8.
[] [PMID: 17440718]
Montgomery SL, Mastrangelo MA, Habib D, et al. Ablation of TNF-RI/RII expression in Alzheimer’s disease mice leads to an unexpected enhancement of pathology: implications for chronic pan-TNF-α suppressive therapeutic strategies in the brain. Am J Pathol 2011; 179(4): 2053-70.
[] [PMID: 21835156]
Tobinick E, Gross H, Weinberger A, Cohen H. TNF-alpha modulation for treatment of Alzheimer’s disease: a 6-month pilot study. MedGenMed 2006; 8(2): 25.
[PMID: 16926764]
Flex A, Giovannini S, Biscetti F, et al. Effect of proinflammatory gene polymorphisms on the risk of Alzheimer’s disease. Neurodegener Dis 2014; 13(4): 230-6.
[PMID: 24022074]
Ribizzi G, Fiordoro S, Barocci S, Ferrari E, Megna M. Cytokine polymorphisms and Alzheimer disease: possible associations. Neurol Sci 2010; 31(3): 321-5.
[] [PMID: 20213229]
Qidwai T, Khan F. Tumour necrosis factor gene polymorphism and disease prevalence. Scand J Immunol 2011; 74(6): 522-47.
[] [PMID: 21790707]
Yang L, Lu R, Jiang L, Liu Z, Peng Y. Expression and genetic analysis of tumor necrosis factor-alpha (TNF-alpha) G-308A polymorphism in sporadic Alzheimer’s disease in a Southern China population. Brain Res 2009; 1247: 178-81.
[] [PMID: 18992723]
Wilson AG, de Vries N, Pociot F, di Giovine FS, van der Putte LB, Duff GW. An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles. J Exp Med 1993; 177(2): 557-60.
[] [PMID: 8426126]
Lio D, Annoni G, Licastro F, et al. Tumor necrosis factor-alpha -308A/G polymorphism is associated with age at onset of Alzheimer’s disease. Mech Ageing Dev 2006; 127(6): 567-71.
[] [PMID: 16516271]
Vural P, Değirmencioğlu S, Parildar-Karpuzoğlu H, 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.
[] [PMID: 19744138]
Lee YH, Choi SJ, Ji JD, Song GG. Association between TNF-α promoter -308 A/G polymorphism and Alzheimer’s disease: a meta-analysis. Neurol Sci 2015; 36(6): 825-32.
[] [PMID: 25647294]
Baranowska-Bik A, Bik W, Wolinska-Witort E, et al. Plasma beta amyloid and cytokine profile in women with Alzheimer’s disease. Neuroendocrinol Lett 2008; 29(1): 75-9.
[PMID: 18283248]
Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhøj P, Pedersen BK. A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci 1999; 54(7): M357-64.
[] [PMID: 10462168]
Kassner SS, Bonaterra GA, Kaiser E, et al. Novel systemic markers for patients with Alzheimer disease? - a pilot study. Curr Alzheimer Res 2008; 5(4): 358-66.
[] [PMID: 18690833]
Zuliani G, Guerra G, Ranzini M, et al. High interleukin-6 plasma levels are associated with functional impairment in older patients with vascular dementia. Int J Geriatr Psychiatry 2007; 22(4): 305-11.
[] [PMID: 17022108]
Alvarez XA, Franco A, Fernández-Novoa L, Cacabelos R. Blood levels of histamine, IL-1 beta, and TNF-alpha in patients with mild to moderate Alzheimer disease. Mol Chem Neuropathol 1996; 29(2-3): 237-52.
[] [PMID: 8971699]
Kim SM, Song J, Kim S, et al. Identification of peripheral inflammatory markers between normal control and Alzheimer’s disease. BMC Neurol 2011; 11: 51.
[] [PMID: 21569380]
Ray S, Britschgi M, Herbert C, et al. Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins. Nat Med 2007; 13(11): 1359-62.
[] [PMID: 17934472]
Björkqvist M, Ohlsson M, Minthon L, Hansson O. Evaluation of a previously suggested plasma biomarker panel to identify Alzheimer’s disease. PLoS One 2012; 7(1)e29868
[] [PMID: 22279551]
Marksteiner J, Kemmler G, Weiss EM, et al. 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(3): 539-40.
[] [PMID: 19395124]
Bermejo P, Martín-Aragón S, Benedí J, et al. Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer’s disease. Immunol Lett 2008; 117(2): 198-202.
[] [PMID: 18367253]
King E, O’Brien JT, Donaghy P, et al. Peripheral inflammation in prodromal Alzheimer’s and Lewy body dementias. J Neurol Neurosurg Psychiatry 2018; 89(4): 339-45.
[] [PMID: 29248892]
Bennet AM, van Maarle MC, Hallqvist J, et al. Association of TNF-α serum levels and TNFA promoter polymorphisms with risk of myocardial infarction. Atherosclerosis 2006; 187(2): 408-14.
[] [PMID: 16243340]
Huizinga TW, Westendorp RG, Bollen EL, et al. TNF-alpha promoter polymorphisms, production and susceptibility to multiple sclerosis in different groups of patients. J Neuroimmunol 1997; 72(2): 149-53.
[] [PMID: 9042107]
Heidari Z, Moudi B, Mahmoudzadeh Sagheb H, Moudi M. Association of TNF-α gene polymorphisms with production of protein and susceptibility to chronic hepatitis B infection in the South East Iranian population. Hepat Mon 2016; 16(11)e41984
[] [PMID: 28070201]
Strle K, Zhou JH, Shen WH, et al. Interleukin-10 in the brain. Crit Rev Immunol 2001; 21(5): 427-49.
[PMID: 11942558]
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.
[] [PMID: 21918553]
Chakrabarty P, Li A, Ceballos-Diaz C, et al. IL-10 alters immunoproteostasis in APP mice, increasing plaque burden and worsening cognitive behavior. Neuron 2015; 85(3): 519-33.
[] [PMID: 25619653]
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.
[] [PMID: 15748779]
Rees LE, Wood NA, Gillespie KM, Lai KN, Gaston K, Mathieson PW. The interleukin-10-1082 G/A polymorphism: allele frequency in different populations and functional significance. Cell Mol Life Sci 2002; 59(3): 560-9.
[] [PMID: 11964134]
Lio D, Licastro F, Scola L, et al. Interleukin-10 promoter polymorphism in sporadic Alzheimer’s disease. Genes Immun 2003; 4(3): 234-8.
[] [PMID: 12700599]
Zhang Y, Zhang J, Tian 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.
[] [PMID: 21255795]
Bagnoli S, Cellini E, Tedde A, et al. Association of IL10 promoter polymorphism in Italian Alzheimer’s disease. Neurosci Lett 2007; 418(3): 262-5.
[] [PMID: 17420099]
Kang HJ, Kim JM, Kim SW, 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.
[] [PMID: 25315113]
Medway C, Combarros O, Cortina-Borja M, et al. The sex-specific associations of the aromatase gene with Alzheimer’s disease and its interaction with IL10 in the Epistasis Project. Eur J Hum Genet 2014; 22(2): 216-20.
[] [PMID: 23736221]
Moraes CF, Benedet AL, Souza VC, et al. Cytokine gene polymorphisms and Alzheimer’s disease in Brazil. Neuroimmunomodulation 2013; 20(5): 239-46.
[] [PMID: 23838435]
Angelopoulos P, Agouridaki H, Vaiopoulos H, et al. Cytokines in Alzheimer’s disease and vascular dementia. Int J Neurosci 2008; 118(12): 1659-72.
[] [PMID: 18937113]
Guillot-Sestier MV, Doty KR, Gate D, et al. Il10 deficiency rebalances innate immunity to mitigate Alzheimer-like pathology. Neuron 2015; 85(3): 534-48.
[] [PMID: 25619654]
Sabbagh JJ, Kinney JW, Cummings JL. Alzheimer’s disease biomarkers: correspondence between human studies and animal models. Neurobiol Dis 2013; 56: 116-30.
[] [PMID: 23631871]
Town T, Vendrame M, Patel A, et al. Reduced Th1 and enhanced Th2 immunity after immunization with Alzheimer’s beta-amyloid(1-42). J Neuroimmunol 2002; 132(1-2): 49-59.
[] [PMID: 12417433]
Kim HD, Tahara K, Maxwell JA, et al. Nasal inoculation of an adenovirus vector encoding 11 tandem repeats of Abeta1-6 upregulates IL-10 expression and reduces amyloid load in a Mo/Hu APPswe PS1dE9 mouse model of Alzheimer’s disease. J Gene Med 2007; 9(2): 88-98.
[] [PMID: 17219449]
Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter . Eur J Immunogenet 1997; 24(1): 1-8..
[ ] [PMID: 9043871]
Miteva L, Stanilova S. The combined effect of interleukin (IL)-10 and IL-12 polymorphisms on induced cytokine production. Hum Immunol 2008; 69(9): 562-6.
[] [PMID: 18703108]
Domingues C, da Cruz E, Silva OAB, Henriques AG, Henriques AG. Impact of cytokines and chemokines on Alzheimer’s Disease neuropathological hallmarks Curr Alzheimer Res 2017; 14(8): 870-82..
[] [PMID: 28317487]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy