Skip to content
2000
Volume 24, Issue 9
  • ISSN: 1871-5273
  • E-ISSN: 1996-3181

Abstract

The most common neurodegenerative illness and leading cause of death in the world is Alzheimer's disease (AD), which is extremely expensive to treat. None of the AD treatments that are currently in the market with approval have any effect on disease progression. However, numerous clinical studies aimed at reducing amyloid beta (Aβ) plaque development, boosting Aβ clearance, or reducing neurofibrillary tangle (NFT) failed or had conflicting results. As oxidative stress (OS), mitochondrial dysfunction, and chronic neuroinflammation are implicated in numerous interconnected vicious cascades, research has revealed new therapeutic targets, including enhancing mitochondrial bioenergetics and quality control, reducing oxidative stress, or modulating neuroinflammatory pathways. This review examines the role of oxidative stress (OS), mitochondrial dysfunction, neuroinflammation, and the interplay between peripheral and central immune systems in the pathogenesis of AD. We highlight how OS and immune dysregulation drive chronic neuroinflammation, exacerbating AD progression. Immune cells and inflammatory molecules emerge as critical players in disease pathology. Overall, this review concludes that targeting OS and immune system crosstalk represents promising therapeutic strategies for mitigating AD progression, providing a foundation for future interventions.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cnsnddt/10.2174/0118715273355336250226055826
2025-03-20
2025-09-11

  • From This Site

    /content/journals/cnsnddt/10.2174/0118715273355336250226055826
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SchainM. KreislW.C. Neuroinflammation in neurodegenerative disorders—A review.Curr. Neurol. Neurosci. Rep.20171732510.1007/s11910‑017‑0733‑228283959
     [Google Scholar]
  2. KwonH.S. KohS.H. Neuroinflammation in neurodegenerative disorders: The roles of microglia and astrocytes.Transl. Neurodegener.2020914210.1186/s40035‑020‑00221‑233239064
     [Google Scholar]
  3. ChenW.W. ZhangX. HuangW.J. Role of neuroinflammation in neurodegenerative diseases (Review).Mol. Med. Rep.20161343391339610.3892/mmr.2016.494826935478
     [Google Scholar]
  4. MasdeuJ.C. PascualB. FujitaM. Imaging neuroinflammation in neurodegenerative disorders.J. Nucl. Med.202263Suppl. 145S52S10.2967/jnumed.121.26320035649654
     [Google Scholar]
  5. LiuT.W. ChenC.M. ChangK.H. Biomarker of neuroinflammation in Parkinson’s disease.Int. J. Mol. Sci.2022238414810.3390/ijms2308414835456966
     [Google Scholar]
  6. RaufA. BadoniH. Abu-IzneidT. Neuroinflammatory markers: Key indicators in the pathology of neurodegenerative diseases.Molecules20222710319410.3390/molecules2710319435630670
     [Google Scholar]
  7. DafnisI. MountakiC. FanariotiE. Temporal pattern of neuroinflammation associated with a low glycemic index diet in the 5xFAD mouse model of alzheimer’s disease.Mol. Neurobiol.202259127303732210.1007/s12035‑022‑03047‑336175825
     [Google Scholar]
  8. XuY. JiangC. WuJ. Ketogenic diet ameliorates cognitive impairment and neuroinflammation in a mouse model of Alzheimer’s disease.CNS Neurosci. Ther.202228458059210.1111/cns.1377934889516
     [Google Scholar]
  9. RichardR. MousaS. Necroptosis in Alzheimer’s disease: Potential therapeutic target.Biomed. Pharmacother.202215211320310.1016/j.biopha.2022.11320335665670
     [Google Scholar]
  10. SinghD. Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer’s disease.J. Neuroinflammation202219120610.1186/s12974‑022‑02565‑035978311
     [Google Scholar]
  11. OnyangoI.G. JaureguiG.V. ČarnáM. BennettJ.P.Jr StokinG.B. Neuroinflammation in Alzheimer’s disease.Biomedicines20219552410.3390/biomedicines905052434067173
     [Google Scholar]
  12. EttchetoM. CanoA. BusquetsO. A metabolic perspective of late onset Alzheimer’s disease.Pharmacol. Res.201914510425510.1016/j.phrs.2019.10425531075308
     [Google Scholar]
  13. NationD.A. SweeneyM.D. MontagneA. Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction.Nat. Med.201925227027610.1038/s41591‑018‑0297‑y30643288
     [Google Scholar]
  14. CanoA. FonsecaE. EttchetoM. Epilepsy in neurodegenerative diseases: Related drugs and molecular pathways.Pharmaceuticals20211410105710.3390/ph1410105734681281
     [Google Scholar]
  15. BhatiaV. SharmaS. Role of mitochondrial dysfunction, oxidative stress and autophagy in progression of Alzheimer’s disease.J. Neurol. Sci.202142111725310.1016/j.jns.2020.11725333476985
     [Google Scholar]
  16. WuK.M. ZhangY.R. HuangY.Y. DongQ. TanL. YuJ.T. The role of the immune system in Alzheimer’s disease.Ageing Res. Rev.20217010140910.1016/j.arr.2021.10140934273589
     [Google Scholar]
  17. LuY. LiK. HuY. WangX. Expression of immune related genes and possible regulatory mechanisms in Alzheimer’s disease.Front. Immunol.20211276896610.3389/fimmu.2021.76896634804058
     [Google Scholar]
  18. SuescunJ. ChandraS. SchiessM.C. The Role of Neuroinflammation in Neurodegenerative Disorders.Academic Press201924126710.1016/B978‑0‑12‑813832‑8.00013‑3
     [Google Scholar]
  19. GuldnerI.H. Wyss-CorayT. Activated immune cells drive neurodegeneration in an Alzheimer’s model.Nature2023615795358858910.1038/d41586‑023‑00600‑536890310
     [Google Scholar]
  20. ZhangQ. YangG. LuoY. JiangL. ChiH. TianG. Neuroinflammation in Alzheimer’s disease: Insights from peripheral immune cells.Immun. Ageing20242113810.1186/s12979‑024‑00445‑038877498
     [Google Scholar]
  21. LiT. LuL. PemberE. LiX. ZhangB. ZhuZ. New insights into neuroinflammation involved in pathogenic mechanism of Alzheimer’s disease and its potential for therapeutic intervention.Cells20221112192510.3390/cells11121925
     [Google Scholar]
  22. JurcăuM.C. Andronie-CioaraF.L. JurcăuA. The link between oxidative stress, mitochondrial dysfunction and neuroinflammation in the pathophysiology of Alzheimer’s disease: Therapeutic implications and future perspectives.Antioxidants20221111216710.3390/antiox1111216736358538
     [Google Scholar]
  23. HenekaM.T. McManusR.M. LatzE. Inflammasome signalling in brain function and neurodegenerative disease.Nat. Rev. Neurosci.2018191061062110.1038/s41583‑018‑0055‑730206330
     [Google Scholar]
  24. CucosC.A. MilanesiE. DobreM. MusatI.A. MandaG. CuadradoA. Altered blood and brain expression of inflammation and redox genes in Alzheimer’s disease, common to APPV717I × TAUP301L mice and patients.Int. J. Mol. Sci.20222310579910.3390/ijms2310579935628609
     [Google Scholar]
  25. TeleanuD.M. NiculescuA.G. LunguI.I. An overview of oxidative stress, neuroinflammation, and neurodegenerative diseases.Int. J. Mol. Sci.20222311593810.3390/ijms2311593835682615
     [Google Scholar]
  26. SimpsonD.S.A. OliverP.L. ROS generation in Microglia: Understanding oxidative stress and inflammation in neurodegenerative disease.Antioxidants20209874310.3390/antiox908074332823544
     [Google Scholar]
  27. WangJ. SongY. ChenZ. LengS.X. Connection between systemic inflammation and neuroinflammation underlies neuroprotective mechanism of several phytochemicals in neurodegenerative diseases.Oxid. Med. Cell. Longev.201820181197271410.1155/2018/197271430402203
     [Google Scholar]
  28. BarreraG. PizzimentiS. DagaM. Lipid peroxidation-derived Aldehydes, 4-Hydroxynonenal and malondialdehyde in aging-related disorders.Antioxidants20187810210.3390/antiox708010230061536
     [Google Scholar]
  29. GrazioliS. PuginJ. Mitochondrial damage-associated molecular patterns: From inflammatory signaling to human diseases.Front. Immunol.2018983210.3389/fimmu.2018.0083229780380
     [Google Scholar]
  30. MisraniA. TabassumS. YangL. Mitochondrial dysfunction and oxidative stress in Alzheimer’s disease.Front. Aging Neurosci.20211361758810.3389/fnagi.2021.61758833679375
     [Google Scholar]
  31. Fanlo-UcarH. Picón-PagèsP. Herrera-FernándezV. ILL-Raga G, Muñoz FJ. The dual role of amyloid beta-peptide in oxidative stress and inflammation: Unveiling their connections in alzheimer’s disease etiopathology.Antioxidants20241310120810.3390/antiox1310120839456461
     [Google Scholar]
  32. IsingC. VenegasC. ZhangS. NLRP3 inflammasome activation drives tau pathology.Nature2019575778466967310.1038/s41586‑019‑1769‑z31748742
     [Google Scholar]
  33. VoetS. SrinivasanS. LamkanfiM. van LooG. Inflammasomes in neuroinflammatory and neurodegenerative diseases.EMBO Mol. Med.2019116e1024810.15252/emmm.20181024831015277
     [Google Scholar]
  34. CummingsJ. ZhouY. LeeG. ZhongK. FonsecaJ. ChengF. Alzheimer’s disease drug development pipeline: 2024.Alzheimers Dement.2024102e1246510.1002/trc2.1246538659717
     [Google Scholar]
  35. HuangX. HussainB. ChangJ. Peripheral inflammation and blood–brain barrier disruption: Effects and mechanisms.CNS Neurosci. Ther.2021271364710.1111/cns.1356933381913
     [Google Scholar]
  36. SongK. LiY. ZhangH. Oxidative stress-mediated blood-brain barrier (BBB) disruption in neurological diseases.Oxid. Med. Cell. Longev.2020202012710.1155/2020/4356386
     [Google Scholar]
  37. ZhaoJ. WangX. HeY. The role of T cells in Alzheimer’s disease pathogenesis.Crit. Rev. Immunol.2023436152310.1615/CritRevImmunol.202305014537943150
     [Google Scholar]
  38. ParkJ.C. HanS.H. Mook-JungI. Peripheral inflammatory biomarkers in Alzheimer’s disease: A brief review.BMB Rep.2020531101910.5483/BMBRep.2020.53.1.30931865964
     [Google Scholar]
  39. JorfiM. Maaser-HeckerA. TanziR.E. The neuroimmune axis of Alzheimer’s disease.Genome Med.2023151610.1186/s13073‑023‑01155‑w36703235
     [Google Scholar]
  40. GateD. SaligramaN. LeventhalO. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease.Nature2020577779039940410.1038/s41586‑019‑1895‑731915375
     [Google Scholar]
  41. Mietelska-PorowskaA. WojdaU. T lymphocytes and inflammatory mediators in the interplay between brain and blood in Alzheimer’s disease: Potential pools of new biomarkers.J. Immunol. Res.2017201711710.1155/2017/462654028293644
     [Google Scholar]
  42. DeMaioA. MehrotraS. SambamurtiK. HusainS. The role of the adaptive immune system and T cell dysfunction in neurodegenerative diseases.J. Neuroinflammation202219125110.1186/s12974‑022‑02605‑936209107
     [Google Scholar]
  43. SunE. MotolaniA. CamposL. LuT. The pivotal role of NF-kB in the pathogenesis and therapeutics of Alzheimer’s disease.Int. J. Mol. Sci.20222316897210.3390/ijms2316897236012242
     [Google Scholar]
  44. MerighiS. NigroM. TravagliA. GessiS. Microglia and Alzheimer’s disease.Int. J. Mol. Sci.202223211299010.3390/ijms23211299036361780
     [Google Scholar]
  45. YetirajamR. KannegantiT.D. Innate immune cell death in neuroinflammation and Alzheimer’s disease.Cells20221112188510.3390/cells11121885
     [Google Scholar]
  46. YangS.H. Cellular and molecular mediators of neuroinflammation in Alzheimer disease.Int. Neurourol. J.201923Suppl. 2S54S6210.5213/inj.1938184.09231795604
     [Google Scholar]
  47. CaiZ. XiaoM. Oligodendrocytes and Alzheimer’s disease.Int. J. Neurosci.2016126297104
     [Google Scholar]
  48. AhmadM.H. FatimaM. MondalA.C. Influence of microglia and astrocyte activation in the neuroinflammatory pathogenesis of Alzheimer’s disease: Rational insights for the therapeutic approaches.J. Clin. Neurosci.20195961110.1016/j.jocn.2018.10.03430385170
     [Google Scholar]
  49. Mandrekar-ColucciS. LandrethG.E. Microglia and inflammation in Alzheimer’s disease.CNS Neurol. Disord. Drug Targets20109215616710.2174/18715271079101207120205644
     [Google Scholar]
  50. AkiyamaH. BargerS. BarnumS. Inflammation and Alzheimer’s disease.Neurobiol. Aging200021338342110.1016/S0197‑4580(00)00124‑X10858586
     [Google Scholar]
  51. CaiZ. YanL.J. RatkaA. Telomere shortening and Alzheimer’s disease.Neuromolecular Med.2013151254810.1007/s12017‑012‑8207‑923161153
     [Google Scholar]
  52. KenigsbuchM. BostP. HaleviS. A shared disease-associated oligodendrocyte signature among multiple CNS pathologies.Nat. Neurosci.202225787688610.1038/s41593‑022‑01104‑735760863
     [Google Scholar]
  53. MoralesI. Guzmán-MartínezL. Cerda-TroncosoC. FaríasG.A. MaccioniR.B. Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches.Front. Cell. Neurosci.2014811210.3389/fncel.2014.0011224795567
     [Google Scholar]
  54. Avila-MuñozE. AriasC. When astrocytes become harmful: Functional and inflammatory responses that contribute to Alzheimer’s disease.Ageing Res. Rev.201418294010.1016/j.arr.2014.07.00425078115
     [Google Scholar]
  55. CaiZ. WanC.Q. LiuZ. Astrocyte and Alzheimer’s disease.J. Neurol.2017264102068207410.1007/s00415‑017‑8593‑x28821953
     [Google Scholar]
  56. KanashiroA. HirokiC.H. da FonsecaD.M. The role of neutrophils in neuro-immune modulation.Pharmacol. Res.202015110458010.1016/j.phrs.2019.10458031786317
     [Google Scholar]
  57. AriesM.L. Hensley-McBainT. Neutrophils as a potential therapeutic target in Alzheimer’s disease.Front. Immunol.202314112314910.3389/fimmu.2023.112314936936930
     [Google Scholar]
  58. ForbesL.H. MironV.E. Monocytes in central nervous system remyelination.Glia202270579780710.1002/glia.2411134708884
     [Google Scholar]
  59. FengY. LiL. SunX.H. Monocytes and Alzheimer’s disease.Neurosci. Bull.201127211512210.1007/s12264‑011‑1205‑321441973
     [Google Scholar]
  60. RichartzsalzburgerE. BatraA. StranskyE. Altered lymphocyte distribution in Alzheimer’s disease.J. Psychiatr. Res.2007411-217417810.1016/j.jpsychires.2006.01.01016516234
     [Google Scholar]
  61. Jadidi-NiaraghF. ShegarfiH. NaddafiF. MirshafieyA. The role of natural killer cells in Alzheimer’s disease.Scand. J. Immunol.201276545145610.1111/j.1365‑3083.2012.02769.x22889057
     [Google Scholar]
  62. Le PageA. DupuisG. FrostE.H. Role of the peripheral innate immune system in the development of Alzheimer’s disease.Exp. Gerontol.2018107596610.1016/j.exger.2017.12.01929275160
     [Google Scholar]
  63. FaridarA. VasquezM. ThomeA.D. Ex vivo expanded human regulatory T cells modify neuroinflammation in a preclinical model of Alzheimer’s disease.Acta Neuropathol. Commun.202210114410.1186/s40478‑022‑01447‑z36180898
     [Google Scholar]
  64. DaiL. ShenY. Insights into T‐cell dysfunction in Alzheimer’s disease.Aging Cell20212012e1351110.1111/acel.1351134725916
     [Google Scholar]
  65. AhnJ.J. Abu-RubM. MillerR.H. B cells in neuroinflammation: New perspectives and mechanistic insights.Cells2021107160510.3390/cells1007160534206848
     [Google Scholar]
  66. MachhiJ. KevadiyaB.D. MuhammadI.K. Harnessing regulatory T cell neuroprotective activities for treatment of neurodegenerative disorders.Mol. Neurodegener.20201513210.1186/s13024‑020‑00375‑732503641
     [Google Scholar]
  67. FengW. ZhangY. DingS. B lymphocytes ameliorate Alzheimer’s disease-like neuropathology via interleukin-35.Brain Behav. Immun.2023108163110.1016/j.bbi.2022.11.01236427805
     [Google Scholar]
  68. KnoxE.G. AburtoM.R. ClarkeG. CryanJ.F. O’DriscollC.M. The blood-brain barrier in aging and neurodegeneration.Mol. Psychiatry2022272659267310.1038/s41380‑022‑01511‑z
     [Google Scholar]
  69. GonzálezH. PachecoR. T-cell-mediated regulation of neuroinflammation involved in neurodegenerative diseases.J. Neuroinflammation201411120110.1186/s12974‑014‑0201‑825441979
     [Google Scholar]
  70. ZenaroE. PiacentinoG. ConstantinG. The blood-brain barrier in Alzheimer’s disease.Neurobiol. Dis.2017107415610.1016/j.nbd.2016.07.00727425887
     [Google Scholar]
  71. LiuC. CuiG. ZhuM. KangX. GuoH. Neuroinflammation in Alzheimer’s disease: Chemokines produced by astrocytes and chemokine receptors.Int. J. Clin. Exp. Pathol.20147128342835525674199
     [Google Scholar]
  72. GuedesJ.R. LaoT. CardosoA.L. El KhouryJ. Roles of microglial and monocyte chemokines and their receptors in regulating Alzheimer’s disease-associated amyloid-β and tau pathologies.Front. Neurol.2018954910.3389/fneur.2018.0054930158892
     [Google Scholar]
  73. ZhuH. YanH. TangN. Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses.Nat. Commun.201781167610.1038/s41467‑017‑01943‑029162816
     [Google Scholar]
  74. WangH. WangX. WangH. WangX. Interleukin 1 receptor and Alzheimer’s disease-related neuroinflammation.In: Mechanisms of Neuroinflammation. InTech201710.5772/intechopen.69067
     [Google Scholar]
  75. LiuX. QuanN. Microglia and CNS interleukin-1: Beyond immunological concepts.Front. Neurol.20189810.3389/fneur.2018.0000829410649
     [Google Scholar]
  76. DinarelloC.A. Overview of the IL ‐1 family in innate inflammation and acquired immunity.Immunol. Rev.2018281182710.1111/imr.1262129247995
     [Google Scholar]
  77. KanekoN. KurataM. YamamotoT. MorikawaS. MasumotoJ. The role of interleukin-1 in general pathology.Inflamm. Regen.2019391210.1186/s41232‑019‑0101‑5
     [Google Scholar]
  78. EscrigA. CanalC. SanchisP. IL-6 trans-signaling in the brain influences the behavioral and physio-pathological phenotype of the Tg2576 and 3xTgAD mouse models of Alzheimer’s disease.Brain Behav. Immun.20198214515910.1016/j.bbi.2019.08.00531401302
     [Google Scholar]
  79. CaiY. LiuJ. WangB. SunM. YangH. Microglia in the neuroinflammatory pathogenesis of Alzheimer’s disease and related therapeutic targets.Front. Immunol.20221385637610.3389/fimmu.2022.85637635558075
     [Google Scholar]
  80. Lobo-SilvaD. CarricheG.M. CastroA.G. RoqueS. SaraivaM. Balancing the immune response in the brain: IL-10 and its regulation.J. Neuroinflammation2016131297
     [Google Scholar]
  81. MagalhãesC.A. CarvalhoM.G. SousaL.P. CaramelliP. GomesK.B. Alzheimer’s disease and cytokine IL-10 gene polymorphisms: Is there an association?Arq. Neuropsiquiatr.201775964965610.1590/0004‑282x2017011028977146
     [Google Scholar]
  82. PorroC. CianciulliA. PanaroM.A. The regulatory role of IL-10 in Neurodegenerative diseases.Biomolecules2020107101710.3390/biom1007101732659950
     [Google Scholar]
  83. WestonL.L. JiangS. ChisholmD. JantzieL.L. BhaskarK. Interleukin-10 deficiency exacerbates inflammation-induced tau pathology.J. Neuroinflammation202118116110.1186/s12974‑021‑02211‑134275478
     [Google Scholar]
  84. JiangH. HampelH. PrvulovicD. Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer’s disease.Mol. Neurodegener.2011616910.1186/1750‑1326‑6‑6921978728
     [Google Scholar]
  85. BelkhelfaM. RafaH. MedjeberO. Arroul-LammaliA. BehairiN. Abada-BendibM. 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.2014341183984710.1089/jir.2013.0085
     [Google Scholar]
  86. JayaramanA. HtikeT.T. JamesR. PiconC. ReynoldsR. TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer’s disease hippocampus.Acta Neuropathol. Commun.20219115910.1186/s40478‑021‑01264‑w34625123
     [Google Scholar]
  87. ZhengC. ZhouX.W. WangJ.Z. The dual roles of cytokines in Alzheimer’s disease: Update on interleukins, TNF-α, TGF-β and IFN-γ.Transl. Neurodegener.201651710.1186/s40035‑016‑0054‑427054030
     [Google Scholar]
  88. GabinJ.M. SaltvedtI. TambsK. HolmenJ. The association of high sensitivity C-reactive protein and incident Alzheimer disease in patients 60 years and older: The HUNT study, Norway.Immun. Ageing2018151410.1186/s12979‑017‑0106‑329387136
     [Google Scholar]
  89. HuangJ. TaoQ. AngT.F.A. The impact of increasing levels of blood C-reactive protein on the inflammatory loci SPI1 and CD33 in Alzheimer’s disease.Transl. Psychiatry202212152310.1038/s41398‑022‑02281‑636550123
     [Google Scholar]
  90. LiuY. ChenX. CheY. LncRNAs as the regulators of brain function and therapeutic targets for Alzheimer’s disease.Aging Dis.202213383785110.14336/AD.2021.111935656102
     [Google Scholar]
  91. GaudetA.D. FonkenL.K. WatkinsL.R. NelsonR.J. PopovichP.G. MicroRNAs: Roles in regulating neuroinflammation.Neuroscientist201824322124510.1177/107385841772115028737113
     [Google Scholar]
  92. KhanI. PreetiK. FernandesV. KhatriD.K. SinghS.B. Role of MicroRNAs, aptamers in neuroinflammation and neurodegenerative disorders.Cell. Mol. Neurobiol.20224272075209510.1007/s10571‑021‑01093‑433934227
     [Google Scholar]
  93. MrakR.E. GriffinW.S.T. Interleukin-1 and the immunogenetics of Alzheimer disease.J. Neuropathol. Exp. Neurol.200059647147610.1093/jnen/59.6.47110850859
     [Google Scholar]
  94. NgA. TamW.W. ZhangM.W. IL-1β, IL-6, TNF- α and CRP in elderly patients with depression or Alzheimer’s disease: Systematic review and meta-analysis.Sci. Rep.2018811205010.1038/s41598‑018‑30487‑630104698
     [Google Scholar]
  95. vom BergJ. ProkopS. MillerK.R. Inhibition of IL-12/IL-23 signaling reduces Alzheimer’s disease–like pathology and cognitive decline.Nat. Med.201218121812181910.1038/nm.296523178247
     [Google Scholar]
  96. BrigasH.C. RibeiroM. CoelhoJ.E. IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease.Cell Rep.202136910957410.1016/j.celrep.2021.10957434469732
     [Google Scholar]
  97. BrowneT.C. McQuillanK. McManusR.M. O’ReillyJ.A. MillsK.H.G. LynchM.A. IFN-γ Production by amyloid β-specific Th1 cells promotes microglial activation and increases plaque burden in a mouse model of Alzheimer’s disease.J. Immunol.201319052241225110.4049/jimmunol.120094723365075
     [Google Scholar]
  98. ChakrabartyP. Ceballos-DiazC. BeccardA. IFN-γ promotes complement expression and attenuates amyloid plaque deposition in amyloid β precursor protein transgenic mice.J. Immunol.201018495333534310.4049/jimmunol.090338220368278
     [Google Scholar]
  99. OuW. YangJ. SimanauskaiteJ. Biologic TNF-α inhibitors reduce microgliosis, neuronal loss, and tau phosphorylation in a transgenic mouse model of tauopathy.J. Neuroinflammation202118131210.1186/s12974‑021‑02332‑734972522
     [Google Scholar]
  100. ZhangH. WeiW. ZhaoM. Interaction between Aβ and Tau in the pathogenesis of Alzheimer’s disease.Int. J. Biol. Sci.20211792181219210.7150/ijbs.5707834239348
     [Google Scholar]
  101. von BernhardiR. CornejoF. ParadaG.E. EugenínJ. Role of TGFβ signaling in the pathogenesis of Alzheimer’s disease.Front. Cell. Neurosci.2015942610.3389/fncel.2015.0042626578886
     [Google Scholar]
  102. ChenJ.H. KeK.F. LuJ.H. QiuY.H. PengY.P. Protection of TGF-β1 against neuroinflammation and neurodegeneration in Aβ1-42-induced Alzheimer’s disease model rats.PLoS One2015102e011654910.1371/journal.pone.011654925658940
     [Google Scholar]
  103. NataleG. CloustonS.A.P. SmithD.M. Elevated C-reactive protein in Alzheimer’s disease without depression in older adults: Findings from the health and retirement study.J. Gerontol. A Biol. Sci. Med. Sci.202277467368210.1093/gerona/glab282
     [Google Scholar]
  104. LicastroF. PedriniS. CaputoL. 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.200010319710210.1016/S0165‑5728(99)00226‑X10674995
     [Google Scholar]
  105. VaresiA. CarraraA. PiresV.G. Blood-based biomarkers for Alzheimer’s disease diagnosis and progression: An overview.Cells2022118136710.3390/cells1108136735456047
     [Google Scholar]
  106. Craig-SchapiroR. PerrinR.J. RoeC.M. YKL-40: A novel prognostic fluid biomarker for preclinical Alzheimer’s disease.Biol. Psychiatry2010681090391210.1016/j.biopsych.2010.08.02521035623
     [Google Scholar]
  107. Villar-PiquéA. SchmitzM. HermannP. Plasma YKL-40 in the spectrum of neurodegenerative dementia.J. Neuroinflammation201916114510.1186/s12974‑019‑1531‑331299989
     [Google Scholar]
  108. SolanaC. TarazonaR. SolanaR. Immunosenescence of natural killer cells, inflammation, and Alzheimer’s disease.Int. J. Alzheimers Dis.201820181910.1155/2018/312875830515321
     [Google Scholar]
  109. Al-GhraiybahN.F. WangJ. AlkhalifaA.E. Glial cell-mediated neuroinflammation in Alzheimer’s disease.Int. J. Mol. Sci.202223181057210.3390/ijms23181057236142483
     [Google Scholar]
  110. Guzman-MartinezL. MaccioniR.B. AndradeV. NavarreteL.P. PastorM.G. Ramos-EscobarN. Neuroinflammation as a common feature of neurodegenerative disorders.Front. Pharmacol.201910100810.3389/fphar.2019.0100831572186
     [Google Scholar]
  111. HuangP.S. TsaiP.Y. YangL.Y. 3,6′-dithiopomalidomide ameliorates hippocampal neurodegeneration, microgliosis and astrogliosis and improves cognitive behaviors in rats with a moderate traumatic brain injury.Int. J. Mol. Sci.20212215827610.3390/ijms2215827634361041
     [Google Scholar]
  112. LiY. XiaX. WangY. ZhengJ.C. Mitochondrial dysfunction in microglia: A novel perspective for pathogenesis of Alzheimer’s disease.J. Neuroinflammation202219124810.1186/s12974‑022‑02613‑936203194
     [Google Scholar]
  113. LiuP. WangY. SunY. PengG. Neuroinflammation as a potential therapeutic target in Alzheimer’s disease.Clin. Interv. Aging20221766567410.2147/CIA.S35755835520949
     [Google Scholar]
  114. RaniV. VermaR. KumarK. ChawlaR. Role of pro-inflammatory cytokines in Alzheimer’s disease and neuroprotective effects of pegylated self-assembled nanoscaffolds.Curr. Res. Pharmacol. Drug Discov.2023410014910.1016/j.crphar.2022.10014936593925
     [Google Scholar]
  115. ItalianiP. PuxedduI. NapoletanoS. Circulating levels of IL-1 family cytokines and receptors in Alzheimer’s disease: New markers of disease progression?J. Neuroinflammation201815134210.1186/s12974‑018‑1376‑130541566
     [Google Scholar]
  116. MausbachB.T. DecastroG. Vara-GarciaC. The relationship between circulating Interleukin-6 levels and future health service use in dementia caregivers.Psychosom. Med.201981766867410.1097/PSY.000000000000071631145377
     [Google Scholar]
  117. Babić LekoM. Nikolac PerkovićM. KlepacN. IL-1β, IL-6, IL-10, and TNFα single nucleotide polymorphisms in human influence the susceptibility to Alzheimer’s disease pathology.J. Alzheimers Dis.20207531029104710.3233/JAD‑20005632390629
     [Google Scholar]
  118. Andronie-CioaraF.L. ArdeleanA.I. Nistor-CseppentoC.D. Molecular mechanisms of neuroinflammation in aging and Alzheimer’s disease progression.Int. J. Mol. Sci.2023243186910.3390/ijms2403186936768235
     [Google Scholar]
  119. SahaS. ButtariB. ProfumoE. TucciP. SasoL. A perspective on Nrf2 signaling pathway for neuroinflammation: A potential therapeutic target in Alzheimer’s and Parkinson’s diseases.Front. Cell. Neurosci.20221578725810.3389/fncel.2021.78725835126058
     [Google Scholar]
  120. ScarianE. ViolaC. DragoniF. Di GerlandoR. RizzoB. DiamantiL. New insights into oxidative stress and inflammatory response in neurodegenerative diseases.Int. J. Mol. Sci.2024255269810.3390/ijms25052698
     [Google Scholar]
  121. GaoH.M. ZhouH. HongJ.S. Oxidative Stress, Neuroinflammation, and Neurodegeneration.Neuroinflammation and Neurodegeneration.New York, NYSpringer20148110410.1007/978‑1‑4939‑1071‑7_5
     [Google Scholar]
  122. PiccaA. CalvaniR. Coelho-JúniorH.J. LandiF. BernabeiR. MarzettiE. Mitochondrial dysfunction, oxidative stress, and neuroinflammation: Intertwined roads to neurodegeneration.Antioxidants20209864710.3390/antiox908064732707949
     [Google Scholar]
  123. FengY. WangX. Antioxidant therapies for Alzheimer’s disease.Oxid. Med. Cell. Longev.2012201211710.1155/2012/47293222888398
     [Google Scholar]
  124. JohnsonDA JohnsonJA Nrf2—a therapeutic target for the treatment of neurodegenerative diseases.Free Radic Biol Med201588Pt B2536710.1016/j.freeradbiomed.2015.07.14726281945
     [Google Scholar]
  125. ZhangG. WangZ. HuH. ZhaoM. SunL. Microglia in Alzheimer’s disease: A target for therapeutic intervention.Front. Cell. Neurosci.20211574958710.3389/fncel.2021.74958734899188
     [Google Scholar]
  126. MiY. QiG. BrintonR.D. YinF. Mitochondria-targeted therapeutics for Alzheimer’s disease: The good, the bad, the potential.Antioxid. Redox Signal.202134861163010.1089/ars.2020.807032143551
     [Google Scholar]
  127. PritamP. DekaR. BhardwajA. Antioxidants in Alzheimer’s disease: Current therapeutic significance and future prospects.Biology202211221210.3390/biology1102021235205079
     [Google Scholar]
  128. JinH. KanthasamyA. GhoshA. AnantharamV. KalyanaramanB. KanthasamyA.G. Mitochondria-targeted antioxidants for treatment of Parkinson’s disease: Preclinical and clinical outcomes.Biochim. Biophys. Acta Mol. Basis Dis.2014184281282129410.1016/j.bbadis.2013.09.00724060637
     [Google Scholar]
  129. ChowdhuryS. ChowdhuryN.S. Novel anti-amyloid-beta (Aβ) monoclonal antibody lecanemab for Alzheimer’s disease: A systematic review.Int. J. Immunopathol. Pharmacol.2023370394632023120983910.1177/0394632023120983937902139
     [Google Scholar]
  130. KlyucherevT.O. OlszewskiP. ShalimovaA.A. Advances in the development of new biomarkers for Alzheimer’s disease.Transl. Neurodegener.20221112510.1186/s40035‑022‑00296‑z35449079
     [Google Scholar]
/content/journals/cnsnddt/10.2174/0118715273355336250226055826
Loading
Oxidative Stress and the Role of Immune Cells in Alzheimer’s Disease: Therapeutic Implications and Future Perspectives
CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 24, 685 (2025); https://doi.org/10.2174/0118715273355336250226055826
/content/journals/cnsnddt/10.2174/0118715273355336250226055826
/content/journals/cnsnddt/10.2174/0118715273355336250226055826
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Alzheimer’s disease; immune cells; interleukins; microglia; Neuroinflammation; oxidative stress; therapeutic targets

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test