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Open Access 01-12-2023 | Alzheimer's Disease | Research

Analysis of complement system and its related factors in Alzheimer’s disease

Authors: Xi-Chen Zhu, Bin-Feng Tang, Meng-Zhuo Zhu, Jing Lu, Han-Xiao Lin, Jia-Ming Tang, Rong Li, Tao Ma

Published in: BMC Neurology | Issue 1/2023

Abstract

Alzheimer’s disease (AD) is a primary cause of dementia. The complement system is closely related to AD pathology and may be a potential target for the prevention and treatment of AD. In our study, we conducted a bioinformatics analysis to analyze the role of the complement system and its related factors in AD using Gene Expression Omnibus (GEO) data. We also conducted a functional analysis. Our study verified that 23 genes were closely related to differentially expressed complement system genes in diseases after intersecting the disease-related complement system module genes and differentially expressed genes. The STRING database was used to predict the interactions between the modular gene proteins of the differential complement system. A total of 21 gene proteins and 44 interaction pairs showed close interactions. We screened key genes and created a diagnostic model. The predictive effect of the model was constructed using GSE5281 and our study indicated that the predictive effect of the model was good. Our study also showed enriched negative regulation of Notch signaling, cytokine secretion involved in the immune response pathway, and cytokine secretion involved in immune response hormone-mediated apoptotic signaling pathway. We hope that our study provides a promising target to prevent and delay the onset, diagnosis, and treatment of AD.

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Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chetelat G, Teunissen CE, et al. Alzheimer’s disease. Lancet. 2021;397(10284):1577–90. https://doi.org/10.1016/S0140-6736(20)32205-4.CrossRefPubMedPubMedCentral

Gate D, Saligrama N, Leventhal O, Yang AC, Unger MS, Middeldorp J, et al. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease. Nature. 2020;577(7790):399–404. https://doi.org/10.1038/s41586-019-1895-7.CrossRefPubMedPubMedCentral

Ahn JJ, Abu-Rub M, Miller RH. B cells in neuroinflammation: new perspectives and mechanistic insights. Cells. 2021;10(7):1605. https://doi.org/10.3390/cells10071605.CrossRefPubMedPubMedCentral

Chen WT, Lu A, Craessaerts K, Pavie B, Sala Frigerio C, Corthout N, et al. Spatial transcriptomics and in situ sequencing to study Alzheimer’s disease. Cell. 2020;182(4):976-91.e19. https://doi.org/10.1016/j.cell.2020.06.038.CrossRefPubMed

Heckmann BL, Teubner BJW, Tummers B, Boada-Romero E, Harris L, Yang M, et al. LC3-associated endocytosis facilitates beta-amyloid clearance and mitigates neurodegeneration in murine Alzheimer’s disease. Cell. 2019;178(3):536-51.e14. https://doi.org/10.1016/j.cell.2019.05.056.CrossRefPubMedPubMedCentral

Lian H, Litvinchuk A, Chiang AC, Aithmitti N, Jankowsky JL, Zheng H. Astrocyte-microglia cross talk through complement activation modulates amyloid pathology in mouse models of Alzheimer’s disease. J Neurosci. 2016;36(2):577–89. https://doi.org/10.1523/JNEUROSCI.2117-15.2016.CrossRefPubMedPubMedCentral

Zhu XC, Dai WZ, Ma T. Impacts of CR1 genetic variants on cerebrospinal fluid and neuroimaging biomarkers in Alzheimer’s disease. BMC Med Genet. 2020;21(1):181. https://doi.org/10.1186/s12881-020-01114-x.CrossRefPubMedPubMedCentral

Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li S, Ramakrishnan S, et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science. 2016;352(6286):712–6. https://doi.org/10.1126/science.aad8373.CrossRefPubMedPubMedCentral

Panitch R, Hu J, Chung J, Zhu C, Meng G, Xia W, et al. Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE epsilon2 protective effect in Alzheimer disease. Mol Psychiatry. 2021;26(10):6054–64. https://doi.org/10.1038/s41380-021-01266-z.CrossRefPubMedPubMedCentral

10.

Hu J, Yang Y, Wang M, Yao Y, Chang Y, He Q, et al. Complement C3a receptor antagonist attenuates tau hyperphosphorylation via glycogen synthase kinase 3beta signaling pathways. Eur J Pharmacol. 2019;850:135–40. https://doi.org/10.1016/j.ejphar.2019.02.020.CrossRefPubMed

11.

Litvinchuk A, Wan YW, Swartzlander DB, Chen F, Cole A, Propson NE, et al. Complement C3aR inactivation attenuates tau pathology and reverses an immune network deregulated in tauopathy models and Alzheimer’s disease. Neuron. 2018;100(6):1337-53.e5. https://doi.org/10.1016/j.neuron.2018.10.031.CrossRefPubMedPubMedCentral

12.

Zhu XC, Liu L, Dai WZ, Ma T. Crry silencing alleviates Alzheimer’s disease injury by regulating neuroinflammatory cytokines and the complement system. Neural Regen Res. 2022;17(8):1841–9. https://doi.org/10.4103/1673-5374.332160.CrossRefPubMedPubMedCentral

13.

Yin C, Ackermann S, Ma Z, Mohanta SK, Zhang C, Li Y, et al. ApoE attenuates unresolvable inflammation by complex formation with activated C1q. Nat Med. 2019;25(3):496–506. https://doi.org/10.1038/s41591-018-0336-8.CrossRefPubMedPubMedCentral

14.

Yang J, Wise L, Fukuchi KI. TLR4 cross-talk with NLRP3 inflammasome and complement signaling pathways in Alzheimer’s disease. Front Immunol. 2020;11:724. https://doi.org/10.3389/fimmu.2020.00724.CrossRefPubMedPubMedCentral

15.

Zhong L, Sheng X, Wang W, Li Y, Zhuo R, Wang K, et al. TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration. Immunity. 2023;56(8):1794-808.e8. https://doi.org/10.1016/j.immuni.2023.06.016.CrossRefPubMed

16.

McGeer EG, McGeer PL. Neuroinflammation in Alzheimer’s disease and mild cognitive impairment: a field in its infancy. J Alzheimers Dis. 2010;19(1):355–61. https://doi.org/10.3233/JAD-2010-1219.CrossRefPubMed

17.

Li Z, Wu H, Luo Y, Tan X. Correlation of serum complement factor 5a level with inflammatory response and cognitive function in patients with Alzheimer’s disease of different severity. BMC Neurol. 2023;23(1):319. https://doi.org/10.1186/s12883-023-03256-w.CrossRefPubMedPubMedCentral

18.

Liu L, Liu X, Zhou J, Wu W, Li X. An improved graph Laplacian regularization method for identifying biomarkers of Alzheimer’s disease. J Theor Biol. 2022;543:111121. https://doi.org/10.1016/j.jtbi.2022.111121.CrossRefPubMed

19.

Barrett T, Suzek TO, Troup DB, Wilhite SE, Ngau WC, Ledoux P, et al. NCBI GEO: mining millions of expression profiles–database and tools. Nucleic Acids Res. 2005;33(Database issue):D562-6. https://doi.org/10.1093/nar/gki022.CrossRefPubMed

20.

Smyth GK. Limma: linear models for microarray data. Bioinformatics and computational biology solutions using R and Bioconductor. 2005. pp. 397–420.

21.

Li D, Cao R, Dong W, Cheng M, Pan X, Hu Z, et al. Identification of potential biomarkers for ankylosing spondylitis based on bioinformatics analysis. BMC Musculoskelet Disord. 2023;24(1):413. https://doi.org/10.1186/s12891-023-06550-3.CrossRefPubMedPubMedCentral

22.

Zhu J, Meng H, Zhang L, Li Y. Exploring the molecular mechanism of comorbidity of autism spectrum disorder and inflammatory bowel disease by combining multiple data sets. J Transl Med. 2023;21(1):372. https://doi.org/10.1186/s12967-023-04218-z.CrossRefPubMedPubMedCentral

23.

Han L, Wang J, Ji XB, Wang ZY, Wang Y, Zhang LY, et al. Transcriptomics analysis identifies the presence of upregulated ribosomal housekeeping genes in the alveolar macrophages of patients with smoking-induced chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2021;16:2653–64. https://doi.org/10.2147/COPD.S313252.CrossRefPubMedPubMedCentral

24.

Davis AP, Grondin CJ, Johnson RJ, Sciaky D, Wiegers J, Wiegers TC, et al. Comparative Toxicogenomics Database (CTD): update 2021. Nucleic Acids Res. 2021;49(D1):D1138–43. https://doi.org/10.1093/nar/gkaa891.CrossRefPubMed

25.

Safran M, Dalah I, Alexander J, Rosen N, Iny Stein T, Shmoish M, et al. GeneCards Version 3: the human gene integrator. Database (Oxford). 2010;2010:baq020. https://doi.org/10.1093/database/baq020.CrossRefPubMed

26.

Zhang Z, Zheng Y, Bian X, Wang M, Chou J, Liu H, et al. Identification of key genes and pathways associated with oxidative stress in periodontitis. Oxid Med Cell Longev. 2022;2022:9728172. https://doi.org/10.1155/2022/9728172.CrossRefPubMedPubMedCentral

27.

Qu S, Liu S, Qiu W, Liu J, Wang H. Screening of autophagy genes as prognostic indicators for glioma patients. Am J Transl Res. 2020;12(9):5320–31.PubMedPubMedCentral

28.

Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559. https://doi.org/10.1186/1471-2105-9-559.CrossRefPubMedPubMedCentral

29.

von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B. STRING: a database of predicted functional associations between proteins. Nucleic Acids Res. 2003;31(1):258–61. https://doi.org/10.1093/nar/gkg034.CrossRef

30.

Dunn PJ, Thomson E, Campbell J, Smith T, Desborough V, Wiser J, et al. ImmPort: shared research data for bioinformatics and immunology. In: 2015 IEEE International Conference on Bioinformatics and Biomedicine (BIBM). IEEE; 2015. pp. 607–10.

31.

Hanzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 2013;14:7. https://doi.org/10.1186/1471-2105-14-7.CrossRefPubMedPubMedCentral

32.

Becht E, Giraldo NA, Lacroix L, Buttard B, Elarouci N, Petitprez F, et al. Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol. 2016;17(1):218. https://doi.org/10.1186/s13059-016-1070-5.CrossRefPubMedPubMedCentral

33.

Liberzon A, Subramanian A, Pinchback R, Thorvaldsdottir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011;27(12):1739–40. https://doi.org/10.1093/bioinformatics/btr260.CrossRefPubMedPubMedCentral

34.

Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009;25(8):1091–3. https://doi.org/10.1093/bioinformatics/btp101.CrossRefPubMedPubMedCentral

35.

Kohl M, Wiese S, Warscheid B. Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol. 2011;696:291–303. https://doi.org/10.1007/978-1-60761-987-1_18.CrossRefPubMed

36.

Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, Berg S, et al. Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry. 2006;63(2):168–74. https://doi.org/10.1001/archpsyc.63.2.168.CrossRefPubMed

37.

Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing. Nat Genet. 2019;51(3):414–30. https://doi.org/10.1038/s41588-019-0358-2.CrossRefPubMedPubMedCentral

38.

Bellenguez C, Kucukali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N, et al. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat Genet. 2022;54(4):412–36. https://doi.org/10.1038/s41588-022-01024-z.CrossRefPubMedPubMedCentral

39.

Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet. 2009;41(10):1094–9. https://doi.org/10.1038/ng.439.CrossRefPubMed

40.

Sims R, van der Lee SJ, Naj AC, Bellenguez C, Badarinarayan N, Jakobsdottir J, et al. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease. Nat Genet. 2017;49(9):1373–84. https://doi.org/10.1038/ng.3916.CrossRefPubMedPubMedCentral

41.

Chatterjee P, Pedrini S, Ashton NJ, Tegg M, Goozee K, Singh AK, et al. Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer’s disease. Alzheimers Dement. 2022;18(6):1141–54. https://doi.org/10.1002/alz.12447.CrossRefPubMed

42.

Benedet AL, Mila-Aloma M, Vrillon A, Ashton NJ, Pascoal TA, Lussier F, et al. Differences between plasma and cerebrospinal fluid glial fibrillary acidic protein levels across the Alzheimer disease continuum. JAMA Neurol. 2021;78(12):1471–83. https://doi.org/10.1001/jamaneurol.2021.3671.CrossRefPubMed

43.

Shi H, Koronyo Y, Rentsendorj A, Regis GC, Sheyn J, Fuchs DT, et al. Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina. Acta Neuropathol. 2020;139(5):813–36. https://doi.org/10.1007/s00401-020-02134-w.CrossRefPubMedPubMedCentral

44.

Miners JS, Schulz I, Love S. Differing associations between Abeta accumulation, hypoperfusion, blood-brain barrier dysfunction and loss of PDGFRB pericyte marker in the precuneus and parietal white matter in Alzheimer’s disease. J Cereb Blood Flow Metab. 2018;38(1):103–15. https://doi.org/10.1177/0271678X17690761.CrossRefPubMed

45.

Wang J, Fan DY, Li HY, He CY, Shen YY, Zeng GH, et al. Dynamic changes of CSF sPDGFRbeta during ageing and AD progression and associations with CSF ATN biomarkers. Mol Neurodegener. 2022;17(1):9. https://doi.org/10.1186/s13024-021-00512-w.CrossRefPubMedPubMedCentral

46.

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. https://doi.org/10.1038/srep12393.CrossRefPubMedPubMedCentral

47.

Pillai JA, Bebek G, Khrestian M, Bena J, Bergmann CC, Bush WS, et al. TNFRSF1B gene variants and related soluble TNFR2 levels impact resilience in Alzheimer’s disease. Front Aging Neurosci. 2021;13:638922. https://doi.org/10.3389/fnagi.2021.638922.CrossRefPubMedPubMedCentral

48.

Brai E, Alina Raio N, Alberi L. Notch1 hallmarks fibrillary depositions in sporadic Alzheimer’s disease. Acta Neuropathol Commun. 2016;4(1):64. https://doi.org/10.1186/s40478-016-0327-2.CrossRefPubMedPubMedCentral

49.

Baron BW, Pytel P. Expression pattern of the BCL6 and ITM2B proteins in normal human brains and in Alzheimer disease. Appl Immunohistochem Mol Morphol. 2017;25(7):489–96. https://doi.org/10.1097/PAI.0000000000000329.CrossRefPubMed

50.

Mancuso R, Fryatt G, Cleal M, Obst J, Pipi E, Monzon-Sandoval J, et al. CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice. Brain. 2019;142(10):3243–64. https://doi.org/10.1093/brain/awz241.CrossRefPubMedPubMedCentral

51.

Folch J, Patraca I, Martinez N, Pedros I, Petrov D, Ettcheto M, et al. The role of leptin in the sporadic form of Alzheimer’s disease. Interactions with the adipokines amylin, ghrelin and the pituitary hormone prolactin. Life Sci. 2015;140:19–28. https://doi.org/10.1016/j.lfs.2015.05.002.CrossRefPubMed

52.

Lin E, Kuo PH, Liu YL, Yang AC, Tsai SJ. Polymorphisms of the DNA repair gene EXO1 modulate cognitive aging in old adults in a Taiwanese population. DNA Repair (Amst). 2019;78:1–6. https://doi.org/10.1016/j.dnarep.2019.03.013.CrossRefPubMed

53.

Nwaobi SE, Cuddapah VA, Patterson KC, Randolph AC, Olsen ML. The role of glial-specific Kir4.1 in normal and pathological states of the CNS. Acta Neuropathol. 2016;132(1):1–21. https://doi.org/10.1007/s00401-016-1553-1.CrossRefPubMedPubMedCentral

54.

Szego EM, Csorba A, Janaky T, Kekesi KA, Abraham IM, Morotz GM, et al. Effects of estrogen on beta-amyloid-induced cholinergic cell death in the nucleus basalis magnocellularis. Neuroendocrinology. 2011;93(2):90–105. https://doi.org/10.1159/000321119.CrossRefPubMed

55.

Soles-Tarres I, Cabezas-Llobet N, Vaudry D, Xifro X. Protective effects of pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide against cognitive decline in neurodegenerative diseases. Front Cell Neurosci. 2020;14:221. https://doi.org/10.3389/fncel.2020.00221.CrossRefPubMedPubMedCentral

56.

Wen YF, Xiao XW, Zhou L, Jiang YL, Zhu Y, Guo LN, et al. Mutations in GBA, SNCA, and VPS35 are not associated with Alzheimer’s disease in a Chinese population: a case-control study. Neural Regen Res. 2022;17(3):682–9. https://doi.org/10.4103/1673-5374.321000.CrossRefPubMed

57.

Katayama T, Sawada J, Takahashi K, Yahara O, Hasebe N. Meta-analysis of cerebrospinal fluid neuron-specific enolase levels in Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Alzheimers Res Ther. 2021;13(1):163. https://doi.org/10.1186/s13195-021-00907-3.CrossRefPubMedPubMedCentral

58.

Lau A, Bourkas M, Lu YQQ, Ostrowski LA, Weber-Adrian D, Figueiredo C, et al. Functional amyloids and their possible influence on Alzheimer disease. Discoveries (Craiova). 2017;5(4):e79. https://doi.org/10.15190/d.2017.9.CrossRefPubMed

59.

Bogdan S, Puscion-Jakubik A, Klimiuk K, Socha K, Kochanowicz J, Gorodkiewicz E. UCHL1 and proteasome in blood serum in relation to dietary habits, concentration of selected antioxidant minerals and total antioxidant status among patients with Alzheimer’s disease. J Clin Med. 2022;11(2):412. https://doi.org/10.3390/jcm11020412.CrossRefPubMedPubMedCentral

60.

Nguyen KV. Encephalomalacia/gliosis, deep venous thrombosis, and cancer in Arg393His antithrombin Hanoi and the potential impact of the beta-amyloid precursor protein (APP) on thrombosis and cancer. AIMS Neurosci. 2022;9(2):175–215. https://doi.org/10.3934/Neuroscience.2022010.CrossRefPubMed

61.

Wu X, Shen Q, Chang H, Li J, Xing D. Promoted CD4(+) T cell-derived IFN-gamma/IL-10 by photobiomodulation therapy modulates neurogenesis to ameliorate cognitive deficits in APP/PS1 and 3xTg-AD mice. J Neuroinflammation. 2022;19(1):253. https://doi.org/10.1186/s12974-022-02617-5.CrossRefPubMedPubMedCentral

62.

Wang Y, Wu X, Deng X, Ma Y, Huang S, Wang Y. Association of CD14-260 (-159) C/T and Alzheimer’s disease: systematic review and trial sequential analyses. J Neural Transm (Vienna). 2018;125(9):1313–8. https://doi.org/10.1007/s00702-018-1896-y.CrossRefPubMed

63.

Shu J, Li N, Wei W, Zhang L. Detection of molecular signatures and pathways shared by Alzheimer’s disease and type 2 diabetes. Gene. 2022;810:146070. https://doi.org/10.1016/j.gene.2021.146070.CrossRefPubMed

64.

Sala Frigerio C, Wolfs L, Fattorelli N, Thrupp N, Voytyuk I, Schmidt I, et al. The major risk factors for Alzheimer’s disease: age, sex, and genes modulate the microglia response to Abeta plaques. Cell Rep. 2019;27(4):1293-306.e6. https://doi.org/10.1016/j.celrep.2019.03.099.CrossRefPubMed

65.

Costa AS, Guerini FR, Arosio B, Galimberti D, Zanzottera M, Bianchi A, et al. SNARE complex polymorphisms associate with alterations of visual selective attention in Alzheimer’s disease. J Alzheimers Dis. 2019;69(1):179–88. https://doi.org/10.3233/JAD-190147.CrossRefPubMed

66.

Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature. 2016;535(7610):153–8. https://doi.org/10.1038/nature18629.CrossRefPubMedPubMedCentral

67.

Markarian M, Krattli RP Jr, Baddour JD, Alikhani L, Giedzinski E, Usmani MT, et al. Glia-selective deletion of complement C1q prevents radiation-induced cognitive deficits and neuroinflammation. Cancer Res. 2021;81(7):1732–44. https://doi.org/10.1158/0008-5472.CAN-20-2565.CrossRefPubMed

68.

Xavier S, Sahu RK, Landes SG, Yu J, Taylor RP, Ayyadevara S, et al. Pericytes and immune cells contribute to complement activation in tubulointerstitial fibrosis. Am J Physiol Renal Physiol. 2017;312(3):F516–32. https://doi.org/10.1152/ajprenal.00604.2016.CrossRefPubMedPubMedCentral

69.

Bai Y, Wang M, Zhao J, Bai H, Zhang X, Wang J, et al. Comparative transcriptome analysis reveals immunoregulation mechanism of lncRNA-mRNA in gill and skin of large yellow croaker (Larimichthys crocea) in response to Cryptocaryon irritans infection. BMC Genomics. 2022;23(1):206. https://doi.org/10.1186/s12864-022-08431-w.CrossRefPubMedPubMedCentral

70.

Yang JX, Maria TC, Zhou B, Xiao FL, Wang M, Mao YJ, et al. Quercetin improves immune function in Arbor Acre broilers through activation of NF-kappaB signaling pathway. Poult Sci. 2020;99(4):2305. https://doi.org/10.1016/j.psj.2020.03.003.CrossRefPubMedPubMedCentral

71.

Qin Y, Sun B, Zhang F, Wang Y, Shen B, Liu Y, et al. Sox7 is involved in antibody-dependent endothelial cell activation and renal allograft injury via the Jagged1-Notch1 pathway. Exp Cell Res. 2019;375(2):20–7. https://doi.org/10.1016/j.yexcr.2019.01.008.CrossRefPubMed

72.

Cumpelik A, Heja D, Hu Y, Varano G, Ordikhani F, Roberto MP, et al. Dynamic regulation of B cell complement signaling is integral to germinal center responses. Nat Immunol. 2021;22(6):757–68. https://doi.org/10.1038/s41590-021-00926-0.CrossRefPubMedPubMedCentral

73.

Bastaert F, Kheir S, Saint-Criq V, Villeret B, Dang PM, El-Benna J, et al. Pseudomonas aeruginosa LasB subverts alveolar macrophage activity by interfering with bacterial killing through downregulation of innate immune defense, reactive oxygen species generation, and complement activation. Front Immunol. 2018;9:1675. https://doi.org/10.3389/fimmu.2018.01675.CrossRefPubMedPubMedCentral

74.

Crowson AN, Magro CM, Usmani A, McNutt NS. Immunoglobulin A-associated lymphocytic vasculopathy: a clinicopathologic study of eight patients. J Cutan Pathol. 2002;29(10):596–601. https://doi.org/10.1034/j.1600-0560.2002.291005.x.CrossRefPubMed

75.

Volk T, Pannicke U, Reisli I, Bulashevska A, Ritter J, Bjorkman A, et al. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency. Hum Mol Genet. 2015;24(25):7361–72. https://doi.org/10.1093/hmg/ddv437.CrossRefPubMedPubMedCentral

76.

Brickshawana A, Hinson SR, Romero MF, Lucchinetti CF, Guo Y, Buttmann M, et al. Investigation of the KIR4.1 potassium channel as a putative antigen in patients with multiple sclerosis: a comparative study. Lancet Neurol. 2014;13(8):795–806. https://doi.org/10.1016/S1474-4422(14)70141-3.CrossRefPubMedPubMedCentral

77.

Riboldi E, Frascaroli G, Transidico P, Luini W, Bernasconi S, Mancini F, et al. Benzydamine inhibits monocyte migration and MAPK activation induced by chemotactic agonists. Br J Pharmacol. 2003;140(2):377–83. https://doi.org/10.1038/sj.bjp.0705428.CrossRefPubMedPubMedCentral

78.

Muk T, Stensballe A, Dmytriyeva O, Brunse A, Jiang PP, Thymann T, et al. Differential brain and cerebrospinal fluid proteomic responses to acute prenatal endotoxin exposure. Mol Neurobiol. 2022;59(4):2204–18. https://doi.org/10.1007/s12035-022-02753-2.CrossRefPubMed

79.

Du T, Li G, Luo H, Pan Y, Xu Q, Ma K. Hippocampal alpha-synuclein mediates depressive-like behaviors. Brain Behav Immun. 2021;95:226–37. https://doi.org/10.1016/j.bbi.2021.03.020.CrossRefPubMed

80.

Leiherer A, Stoemmer K, Muendlein A, Saely CH, Kinz E, Brandtner EM, et al. Quercetin impacts expression of metabolism- and obesity-associated genes in SGBS adipocytes. Nutrients. 2016;8(5):282. https://doi.org/10.3390/nu8050282.CrossRefPubMedPubMedCentral

81.

Chen ZM, Cui Q, Zhao B, Song R, Zhang X, Yoshie O. SST: spatial and semantic transformers for multi-label image recognition. IEEE Trans Image Process. 2022;31:2570–83. https://doi.org/10.1109/TIP.2022.3148867.CrossRefPubMed

82.

Melms A, Malcherek G, Gern U, Sommer N, Weissert R, Wietholter H, et al. Thymectomy and azathioprine have no effect on the phenotype of CD4 T lymphocyte subsets in myasthenia gravis. J Neurol Neurosurg Psychiatry. 1993;56(1):46–51. https://doi.org/10.1136/jnnp.56.1.46.CrossRefPubMedPubMedCentral

83.

Mejia JE, Willmott A, Levy E, Earnshaw WC, Larin Z. Functional complementation of a genetic deficiency with human artificial chromosomes. Am J Hum Genet. 2001;69(2):315–26. https://doi.org/10.1086/321977.CrossRefPubMedPubMedCentral

84.

Yoon YH, Hwang HJ, Sung HJ, Heo SH, Kim DS, Hong SH, et al. Upregulation of complement factor H by SOCS-1/3(-)STAT4 in lung cancer. Cancers (Basel). 2019;11(4):471. https://doi.org/10.3390/cancers11040471.CrossRefPubMed

85.

Thomas AM, Gerogianni A, McAdam MB, Floisand Y, Lau C, Espevik T, et al. Complement component C5 and TLR molecule CD14 mediate heme-induced thromboinflammation in human blood. J Immunol. 2019;203(6):1571–8. https://doi.org/10.4049/jimmunol.1900047.CrossRefPubMedPubMedCentral

86.

Cai XY, Wang ZF, Ge SW, Xu G. Identification of hub genes and immune-related pathways for membranous nephropathy by bioinformatics analysis. Front Physiol. 2022;13:914382. https://doi.org/10.3389/fphys.2022.914382.CrossRefPubMedPubMedCentral

87.

De Schepper S, Ge JZ, Crowley G, Ferreira LSS, Garceau D, Toomey CE, et al. Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer’s disease. Nat Neurosci. 2023. https://doi.org/10.1038/s41593-023-01257-z.CrossRefPubMedPubMedCentral

88.

Ekinci IB, Hizal M, Emiralioglu N, Ozcelik U, Yalcin E, Dogru D, et al. Differentially expressed genes associated with disease severity in siblings with cystic fibrosis. Pediatr Pulmonol. 2021;56(5):910–20. https://doi.org/10.1002/ppul.25237.CrossRefPubMed

89.

Santonicola P, Germoglio M, d’Abbusco DS, Adamo A. Functional characterization of Caenorhabditis elegans cbs-2 gene during meiosis. Sci Rep. 2020;10(1):20913. https://doi.org/10.1038/s41598-020-78006-w.CrossRefPubMedPubMedCentral

90.

Altuna-Azkargorta M, Mendioroz-Iriarte M. Blood biomarkers in Alzheimer’s disease. Neurologia (Engl Ed). 2021;36(9):704–10. https://doi.org/10.1016/j.nrleng.2018.03.006.CrossRefPubMed

91.

Zhang Q, Li J, Weng L. Identification and validation of aging-related genes in Alzheimer’s disease. Front Neurosci. 2022;16:905722. https://doi.org/10.3389/fnins.2022.905722.CrossRefPubMedPubMedCentral

92.

Deng Y, Feng Y, Lv Z, He J, Chen X, Wang C, et al. Machine learning models identify ferroptosis-related genes as potential diagnostic biomarkers for Alzheimer’s disease. Front Aging Neurosci. 2022;14:994130. https://doi.org/10.3389/fnagi.2022.994130.CrossRefPubMedPubMedCentral

93.

Yuan M, Feng Y, Zhao M, Xu T, Li L, Guo K, et al. Identification and verification of genes associated with hypoxia microenvironment in Alzheimer’s disease. Sci Rep. 2023;13(1):16252. https://doi.org/10.1038/s41598-023-43595-9.CrossRefPubMedPubMedCentral

94.

Wang H, Zhang Y, Zheng C, Yang S, Chen X, Wang H, et al. A 3-gene-based diagnostic signature in Alzheimer’s disease. Eur Neurol. 2022;85(1):6–13. https://doi.org/10.1159/000518727.CrossRefPubMed

95.

Hu D, Mo X, Jihang L, Huang C, Xie H, Jin L. Novel diagnostic biomarkers of oxidative stress, immunological characterization and experimental validation in Alzheimer’s disease. Aging (Albany NY). 2023;15(19):10389–406. https://doi.org/10.18632/aging.205084.CrossRefPubMed

96.

Lin Y, Zhang L, Gao M, Tang Z, Cheng X, Li H, et al. miR-6076 targets BCL6 in SH-SY5Y cells to regulate amyloid-beta-induced neuronal damage. J Cell Mol Med. 2023. https://doi.org/10.1111/jcmm.17999.CrossRefPubMedPubMedCentral

97.

Song M, Xiong JX, Wang YY, Tang J, Zhang B, Bai Y. VIP enhances phagocytosis of fibrillar beta-amyloid by microglia and attenuates amyloid deposition in the brain of APP/PS1 mice. PLoS One. 2012;7(2):e29790. https://doi.org/10.1371/journal.pone.0029790.CrossRefPubMedPubMedCentral

98.

Lemercier P, Vergallo A, Lista S, Zetterberg H, Blennow K, Potier MC, et al. Association of plasma Abeta40/Abeta42 ratio and brain Abeta accumulation: testing a whole-brain PLS-VIP approach in individuals at risk of Alzheimer’s disease. Neurobiol Aging. 2021;107:57–69. https://doi.org/10.1016/j.neurobiolaging.2021.07.005.CrossRefPubMed

Title: Analysis of complement system and its related factors in Alzheimer’s disease
Authors: Xi-Chen Zhu
Bin-Feng Tang
Meng-Zhuo Zhu
Jing Lu
Han-Xiao Lin
Jia-Ming Tang
Rong Li
Tao Ma
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Alzheimer's Disease
Alzheimer's Disease
Published in: BMC Neurology / Issue 1/2023
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-023-03503-0

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Analysis of complement system and its related factors in Alzheimer’s disease

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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