Skip to content
2000
Volume 22, Issue 6
  • ISSN: 1567-2050
  • E-ISSN: 1875-5828
file format pdf download PDF
file format text download EPUB
side by side viewer icon HTML

Abstract

Oligodendrocytes (OLs) are the primary myelinating cells in the central nervous system (CNS), responsible for maintaining the rapid conduction of nerve signals and ensuring neuronal stability through metabolic and nutritional support. Recent studies have reported that OLs are also involved in the development and progression of Alzheimer's disease (AD), particularly in the production and clearance of amyloid-beta (Aβ), exhibiting complex and critical regulatory functions. While traditional research has predominantly focused on the roles of neurons and microglia in Aβ metabolism, recent evidence indicates that OLs engage in a complex bidirectional interaction with Aβ in AD. On the one hand, OLs can produce Aβ, frequently generating aggregated and highly toxic Aβ, which contributes to plaque expansion and disease progression. On the other hand, neuron-derived Aβ exerts a concentration-dependent dual effect on OLs. At high concentrations, it induces oxidative stress and cell apoptosis, while at low concentrations, it promotes their differentiation and myelin repair functions. Therefore, OLs serve as both a “source” and a “target” of Aβ production and response, making them a key factor in AD pathogenesis. This review discusses the interaction between OLs and Aβ in AD, aiming to provide new perspectives on targeting OLs for AD therapy. Given the dual role of OLs in Aβ metabolism, targeting OLs dysfunction and the regulatory mechanisms underlying Aβ production and clearance could provide novel therapeutic strategies for AD. Future research should investigate the roles of specific OL populations (including oligodendrocyte precursor cells (OPCs), pre-myelinating OLs, and mature OLs) in Aβ generation and metabolism, focusing on the signaling pathways involved. Additionally, the molecular mechanisms by which OLs regulate other glial cells, such as astrocytes and microglia, through intercellular signaling to facilitate Aβ clearance and maintain neuroglial homeostasis warrant further exploration.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/car/10.2174/0115672050401966250625171338
2025-07-07
2025-10-29

  • From This Site

    /content/journals/car/10.2174/0115672050401966250625171338
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/car/22/6/CAR-22-6-01.html?itemId=/content/journals/car/10.2174/0115672050401966250625171338&mimeType=html&fmt=ahah

References

  1. Zyuz’kovG.N. MiroshnichenkoL.A. ChayikovskyiA.V. Kotlov-skayaL.Y. Nf-κb: A target for synchronizing the functioning nervous tissue progenitors of different types in Alzheimer’s disease.Curr. Mol. Pharmacol.202316223424110.2174/1874467215666220601144727 35652396
     [Google Scholar]
  2. WangW. MinJ. LuoQ. GuX. LiM. LiuX. Lysine acetyltransferase TIP60 restricts nerve injury by activating ikkβ/snap23 axis‐mediated autophagosome‐lysosome fusion in Alzheimer’s disease.CNS Neurosci. Ther.20243011e7009510.1111/cns.70095 39500626
     [Google Scholar]
  3. YuL. CheR. ZhangW. Cornuside, by regulating the AGEs‐RAGE‐IκBα‐ERK1/2 signaling pathway, ameliorates cognitive impairment associated with brain aging.Phytother. Res.20233762419243610.1002/ptr.7765 36781177
     [Google Scholar]
  4. ShaoN. DingZ. LiuF. Huang-Pu-Tong-Qiao formula alleviates hippocampal neuron damage by inhibiting nlrp3 inflammasome-mediated pyroptosis in Alzheimer’s Disease.Mol. Neurobiol.20256244545456110.1007/s12035‑024‑04547‑0 39466576
     [Google Scholar]
  5. ZiarR. TesarP.J. ClaytonB.L.L. Astrocyte and oligodendrocyte pathology in Alzheimer’s disease.Neurotherapeutics2025223e0054010.1016/j.neurot.2025.e00540 39939240
     [Google Scholar]
  6. KediaS. SimonsM. Oligodendrocytes in Alzheimer’s disease pathophysiology.Nat. Neurosci.202528344645610.1038/s41593‑025‑01873‑x 39881195
     [Google Scholar]
  7. LiuX. LvZ. HuangQ. LeiY. LiuH. XuP. The role of oligodendrocyte lineage cells in the pathogenesis of Alzheimer’s disease.Neurochem. Res.20255017210.1007/s11064‑024‑04325‑3 39751972
     [Google Scholar]
  8. NoceraS. ChanJ.R. Remyelination by preexisting oligodendrocytes: Glass half full or half empty?Neuron2023111111689169110.1016/j.neuron.2023.05.001 37290399
     [Google Scholar]
  9. KirbyL. Castelo-BrancoG. Crossing boundaries: Interplay between the immune system and oligodendrocyte lineage cells.Semin. Cell Dev. Biol.2021116455210.1016/j.semcdb.2020.10.013 33162336
     [Google Scholar]
  10. NarineM. ColognatoH. Current insights into oligodendrocyte metabolism and its power to sculpt the myelin landscape.Front. Cell. Neurosci.20221689296810.3389/fncel.2022.892968 35573837
     [Google Scholar]
  11. TepavčevićV. Oligodendroglial energy metabolism and (re)Myelination.Life202111323810.3390/life11030238 33805670
     [Google Scholar]
  12. SpiethL. SimonsM. Remember oligodendrocytes: Uncovering their overlooked role in Alzheimer’s disease.PLoS Biol.2024229e300279810.1371/journal.pbio.3002798 39264958
     [Google Scholar]
  13. SunX-H. DongY. X, Zhang H.Y, Li H.Y, Liu P.H, Sui Y. Association between Alzheimer’s disease pathogenesis and early demyelination and oligodendrocyte dysfunction.Neural Regen. Res.201813590891410.4103/1673‑5374.232486 29863022
     [Google Scholar]
  14. ChenJ.F. LiuK. HuB. Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer’s disease.Neuron20211091422922307.e510.1016/j.neuron.2021.05.012 34102111
     [Google Scholar]
  15. von BartheldC.S. BahneyJ. Herculano-HouzelS. The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting.J. Comp. Neurol.2016524183865389510.1002/cne.24040 27187682
     [Google Scholar]
  16. SimonsM. GibsonE.M. NaveK.A. Oligodendrocytes: Myelination, plasticity, and axonal support.Cold Spring Harb. Perspect. Biol.20241610a04135910.1101/cshperspect.a041359 38621824
     [Google Scholar]
  17. OsanaiY. YamazakiR. ShinoharaY. OhnoN. Heterogeneity and regulation of oligodendrocyte morphology.Front. Cell Dev. Biol.202210103048610.3389/fcell.2022.1030486 36393856
     [Google Scholar]
  18. Pérez-CerdáF. Sánchez-GómezM.V. MatuteC. Pío del Río Hortega and the discovery of the oligodendrocytes.Front. Neuroanat.201599210.3389/fnana.2015.00092 26217196
     [Google Scholar]
  19. OsanaiY. ShimizuT. MoriT. Rabies virus‐mediated oligodendrocyte labeling reveals a single oligodendrocyte myelinates axons from distinct brain regions.Glia20176519310510.1002/glia.23076 27759175
     [Google Scholar]
  20. KuhnS. GrittiL. CrooksD. DombrowskiY. Oligodendrocytes in development, myelin generation and beyond.Cells2019811142410.3390/cells8111424 31726662
     [Google Scholar]
  21. TianeA. SchepersM. RombautB. From OPC to Oligodendrocyte: An Epigenetic Journey.Cells2019810123610.3390/cells8101236 31614602
     [Google Scholar]
  22. HughesE.G. Orthmann-MurphyJ.L. LangsethA.J. BerglesD.E. Myelin remodeling through experience-dependent oligodendrogenesis in the adult somatosensory cortex.Nat. Neurosci.201821569670610.1038/s41593‑018‑0121‑5 29556025
     [Google Scholar]
  23. FranklinR.J.M. FrisénJ. LyonsD.A. Revisiting remyelination: Towards a consensus on the regeneration of CNS myelin.Semin. Cell Dev. Biol.20211163910.1016/j.semcdb.2020.09.009 33082115
     [Google Scholar]
  24. BercuryK.K. MacklinW.B. Dynamics and mechanisms of CNS myelination.Dev. Cell201532444745810.1016/j.devcel.2015.01.016 25710531
     [Google Scholar]
  25. FünfschillingU. SupplieL.M. MahadD. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity.Nature2012485739951752110.1038/nature11007 22622581
     [Google Scholar]
  26. LeeY. MorrisonB.M. LiY. Oligodendroglia metabolically support axons and contribute to neurodegeneration.Nature2012487740844344810.1038/nature11314 22801498
     [Google Scholar]
  27. MunyeshyakaM. FieldsR.D. Oligodendroglia are emerging players in several forms of learning and memory.Commun. Biol.202251114810.1038/s42003‑022‑04116‑y 36309567
     [Google Scholar]
  28. ChenW.T. LuA. CraessaertsK. Spatial transcriptomics and in situ sequencing to study Alzheimer’s disease.Cell20201824976991.e1910.1016/j.cell.2020.06.038 32702314
     [Google Scholar]
  29. GrubmanA. ChewG. OuyangJ.F. A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation.Nat. Neurosci.201922122087209710.1038/s41593‑019‑0539‑4 31768052
     [Google Scholar]
  30. MathysH. Davila-VelderrainJ. PengZ. Single-cell transcriptomic analysis of Alzheimer’s disease.Nature2019570776133233710.1038/s41586‑019‑1195‑2 31042697
     [Google Scholar]
  31. İşÖ. MinY. WangX. OatmanS.R. DanielA.A. Ertekin-TanerN. Multi layered omics approaches reveal glia specific alterations in Alzheimer’s disease: A systematic review and future prospects.Glia202573353957310.1002/glia.24652 39652363
     [Google Scholar]
  32. ZhouY. SongW.M. AndheyP.S. Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease.Nat. Med.202026113114210.1038/s41591‑019‑0695‑9 31932797
     [Google Scholar]
  33. GuL. WuD. TangX. Myelin changes at the early stage of 5XFAD mice.Brain Res. Bull.201813728529310.1016/j.brainresbull.2017.12.013 29288735
     [Google Scholar]
  34. AngeliS. KousiappaI. StavrouM. Altered expression of glial gap junction proteins Cx43, Cx30, and Cx47 in the 5XFAD model of Alzheimer’s Disease.Front. Neurosci.20201458293410.3389/fnins.2020.582934 33117125
     [Google Scholar]
  35. DeppC. SunT. SasmitaA.O. Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease.Nature2023618796434935710.1038/s41586‑023‑06120‑6 37258678
     [Google Scholar]
  36. ZhangX. WangR. HuD. Oligodendroglial glycolytic stress triggers inflammasome activation and neuropathology in Alzheimer’s disease.Sci. Adv.2020649eabb868010.1126/sciadv.abb8680 33277246
     [Google Scholar]
  37. KenigsbuchM. BostP. HaleviS. A shared disease-associated oligodendrocyte signature among multiple CNS pathologies.Nat. Neurosci.202225787688610.1038/s41593‑022‑01104‑7 35760863
     [Google Scholar]
  38. PandeyS. ShenK. LeeS.H. Disease-associated oligodendrocyte responses across neurodegenerative diseases.Cell Rep.202240811118910.1016/j.celrep.2022.111189 36001972
     [Google Scholar]
  39. KarranE. De StrooperB. The amyloid hypothesis in Alzheimer disease: New insights from new therapeutics.Nat. Rev. Drug Discov.202221430631810.1038/s41573‑022‑00391‑w 35177833
     [Google Scholar]
  40. Le BrasA. Role of oligodendrocytes in Aβ plaque burden.Lab Anim. (NY)202453922210.1038/s41684‑024‑01437‑9 39215171
     [Google Scholar]
  41. ZhangY. ChenK. SloanS.A. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex.J. Neurosci.20143436119291194710.1523/JNEUROSCI.1860‑14.2014 25186741
     [Google Scholar]
  42. SharmaK. SchmittS. BergnerC.G. Cell type– and brain region–resolved mouse brain proteome.Nat. Neurosci.201518121819183110.1038/nn.4160 26523646
     [Google Scholar]
  43. RajaniR.M. EllingfordR. HellmuthM. Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease.PLoS Biol.2024227e300272710.1371/journal.pbio.3002727 39042667
     [Google Scholar]
  44. EhrlichM. MozafariS. GlatzaM. Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors.Proc. Natl. Acad. Sci. USA201711411E2243E225210.1073/pnas.1614412114 28246330
     [Google Scholar]
  45. ShiY. KirwanP. LiveseyF.J. Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks.Nat. Protoc.20127101836184610.1038/nprot.2012.116 22976355
     [Google Scholar]
  46. DawkinsE. DerksR.J.E. SchiffererM. Membrane lipid remodeling modulates γ-secretase processivity.J. Biol. Chem.2023299410302710.1016/j.jbc.2023.103027 36805335
     [Google Scholar]
  47. HurJ.Y. γ-Secretase in Alzheimer’s disease.Exp. Mol. Med.202254443344610.1038/s12276‑022‑00754‑8 35396575
     [Google Scholar]
  48. StadelmannC. TimmlerS. Barrantes-FreerA. SimonsM. Myelin in the central nervous system: Structure, function, and pathology.Physiol. Rev.20199931381143110.1152/physrev.00031.2018 31066630
     [Google Scholar]
  49. JankowskyJ.L. FadaleD.J. AndersonJ. Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase.Hum. Mol. Genet.200413215917010.1093/hmg/ddh019 14645205
     [Google Scholar]
  50. DuffK. EckmanC. ZehrC. Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1.Nature1996383660271071310.1038/383710a0 8878479
     [Google Scholar]
  51. De StrooperB. SaftigP. CraessaertsK. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein.Nature1998391666538739010.1038/34910 9450754
     [Google Scholar]
  52. HerremanA. HartmannD. AnnaertW. Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency.Proc. Natl. Acad. Sci. USA19999621118721187710.1073/pnas.96.21.11872 10518543
     [Google Scholar]
  53. LeeJ.H. YangD.S. GoulbourneC.N. Faulty autolysosome acidification in Alzheimer’s disease mouse models induces autophagic build-up of Aβ in neurons, yielding senile plaques.Nat. Neurosci.202225668870110.1038/s41593‑022‑01084‑8 35654956
     [Google Scholar]
  54. PensalfiniA. AlbayR. RasoolS. Intracellular amyloid and the neuronal origin of Alzheimer neuritic plaques.Neurobiol. Dis.201471536110.1016/j.nbd.2014.07.011 25092575
     [Google Scholar]
  55. BeroA.W. YanP. RohJ.H. Neuronal activity regulates the regional vulnerability to amyloid-β deposition.Nat. Neurosci.201114675075610.1038/nn.2801 21532579
     [Google Scholar]
  56. SullivanS.M. LeeA. BjörkmanS.T. Cytoskeletal anchoring of GLAST determines susceptibility to brain damage: an identified role for GFAP.J. Biol. Chem.200728240294142942310.1074/jbc.M704152200 17684014
     [Google Scholar]
  57. GoursaudS. KozlovaE.N. MaloteauxJ.M. HermansE. Cultured astrocytes derived from corpus callosum or cortical grey matter show distinct glutamate handling properties.J. Neurochem.200910861442145210.1111/j.1471‑4159.2009.05889.x 19222709
     [Google Scholar]
  58. LevitA. RegisA.M. GibsonA. Impaired behavioural flexibility related to white matter microgliosis in the TgAPP21 rat model of Alzheimer disease.Brain Behav. Immun.201980253410.1016/j.bbi.2019.02.013 30776475
     [Google Scholar]
  59. FerreiraS. PitmanK.A. WangS. Amyloidosis is associated with thicker myelin and increased oligodendrogenesis in the adult mouse brain.J. Neurosci. Res.202098101905193210.1002/jnr.24672 32557778
     [Google Scholar]
  60. AiresV. Ziegler-WaldkirchS. FriesenM. Seed-induced Aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer’s disease.Front. Cell. Neurosci.20221686291810.3389/fncel.2022.862918 36003141
     [Google Scholar]
  61. JantaratnotaiN. RyuJ.K. KimS.U. McLarnonJ.G. Amyloid β peptide-induced corpus callosum damage and glial activation in vivo.Neuroreport200314111429143310.1097/00001756‑200308060‑00005 12960758
     [Google Scholar]
  62. OkechukwuN.G. KleinC. JamannH. MaitreM. Patte-MensahC. Mensah-NyaganA.G. Monomeric amyloid peptide-induced toxicity in human oligodendrocyte cell line and mouse brain primary mixed-glial cell cultures: Evidence for a neuroprotective effect of neurosteroid 3α-O-allyl-allopregnanolone.Neurotox. Res.20244243710.1007/s12640‑024‑00715‑1 39102123
     [Google Scholar]
  63. Al-MashhadiS. SimpsonJ.E. HeathP.R. Oxidative glial cell damage associated with white matter lesions in the aging human brain.Brain Pathol.201525556557410.1111/bpa.12216 25311358
     [Google Scholar]
  64. TseK.H. DNA damage in the oligodendrocyte lineage and its role in brain aging.Mechanism Ageing Devel2017161375010.1016/j.mad.2016.05.006
     [Google Scholar]
  65. BehrendtG. BaerK. BuffoA. Dynamic changes in myelin aberrations and oligodendrocyte generation in chronic amyloidosis in mice and men.Glia201361227328610.1002/glia.22432 23090919
     [Google Scholar]
  66. SubasingheS. UnabiaS. BarrowC.J. MokS.S. AguilarM.I. SmallD.H. Cholesterol is necessary both for the toxic effect of Aβ peptides on vascular smooth muscle cells and for Aβ binding to vascular smooth muscle cell membranes.J. Neurochem.200384347147910.1046/j.1471‑4159.2003.01552.x 12558967
     [Google Scholar]
  67. Collins-PrainoL.E. FrancisY.I. GriffithE.Y. Soluble amyloid beta levels are elevated in the white matter of Alzheimer’s patients, independent of cortical plaque severity.Acta Neuropathol. Commun.2014218310.1186/s40478‑014‑0083‑0 25129614
     [Google Scholar]
  68. HolmesC. BocheD. WilkinsonD. Long-term effects of Aβ42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial.Lancet2008372963421622310.1016/S0140‑6736(08)61075‑2 18640458
     [Google Scholar]
  69. SelkoeD.J. Resolving controversies on the path to Alzheimer’s therapeutics.Nat. Med.20111791060106510.1038/nm.2460 21900936
     [Google Scholar]
  70. LeeJ.T. XuJ. LeeJ.M. Amyloid-β peptide induces oligodendrocyte death by activating the neutral sphingomyelinase–ceramide pathway.J. Cell Biol.2004164112313110.1083/jcb.200307017 14709545
     [Google Scholar]
  71. DesaiM.K. GuercioB.J. NarrowW.C. BowersW.J. An Alzheimer’s disease‐relevant presenilin‐1 mutation augments amyloid‐beta‐induced oligodendrocyte dysfunction.Glia201159462764010.1002/glia.21131 21294162
     [Google Scholar]
  72. DesaiM.K. MastrangeloM.A. RyanD.A. SudolK.L. NarrowW.C. BowersW.J. Early oligodendrocyte/myelin pathology in Alzheimer’s disease mice constitutes a novel therapeutic target.Am. J. Pathol.201017731422143510.2353/ajpath.2010.100087 20696774
     [Google Scholar]
  73. XuJ. ChenS. AhmedS.H. Amyloid-beta peptides are cytotoxic to oligodendrocytes.J. Neurosci.2001211RC11810.1523/JNEUROSCI.21‑01‑j0001.2001 11150354
     [Google Scholar]
  74. RothA.D. RamírezG. AlarcónR. Von BernhardiR. Oligodendrocytes damage in Alzheimer’s disease: Beta amyloid toxicity and inflammation.Biol. Res.200538438138710.4067/S0716‑97602005000400011 16579521
     [Google Scholar]
  75. HoriuchiM. MaezawaI. ItohA. Amyloid β1–42 oligomer inhibits myelin sheet formation in vitro.Neurobiol. Aging201233349950910.1016/j.neurobiolaging.2010.05.007 20594620
     [Google Scholar]
  76. McCanneyG.A. McGrathM.A. OttoT.D. Low sulfated heparins target multiple proteins for central nervous system repair.Glia201967466868710.1002/glia.23562 30585359
     [Google Scholar]
  77. TruongP.H. CiccotostoG.D. MersonT.D. Amyloid precursor protein and amyloid precursor‐like protein 2 have distinct roles in modulating myelination, demyelination, and remyelination of axons.Glia201967352553810.1002/glia.23561 30506868
     [Google Scholar]
  78. ZotaI. ChanoumidouK. GravanisA. CharalampopoulosI. Stimulating myelin restoration with BDNF: a promising therapeutic approach for Alzheimer’s disease.Front. Cell. Neurosci.202418142213010.3389/fncel.2024.1422130 39285941
     [Google Scholar]
  79. Quintela-LópezT. Ortiz-SanzC. Serrano-RegalM.P. Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling.Cell Death Dis.201910644510.1038/s41419‑019‑1636‑8 31171765
     [Google Scholar]
  80. WaggenerC.T. DupreeJ.L. ElgersmaY. FussB. CaMKIIβ regulates oligodendrocyte maturation and CNS myelination.J. Neurosci.20133325104531045810.1523/JNEUROSCI.5875‑12.2013 23785157
     [Google Scholar]
  81. MüllerC. BauerN.M. SchäferI. WhiteR. Making myelin basic protein -from mRNA transport to localized translation.Front. Cell. Neurosci.2013716910.3389/fncel.2013.00169 24098271
     [Google Scholar]
  82. NygaardH.B. van DyckC.H. StrittmatterS.M. Fyn kinase inhibition as a novel therapy for Alzheimer’s disease.Alzheimers Res. Ther.201461810.1186/alzrt238 24495408
     [Google Scholar]
  83. MeurS. KaratiD. Fyn kinase in Alzheimer’s disease: Unraveling molecular mechanisms and therapeutic implications.Mol. Neurobiol.202562164366010.1007/s12035‑024‑04286‑2 38890236
     [Google Scholar]
  84. IshiiA. PathoulasJ.A. OmarM.O. Contribution of amyloid deposition from oligodendrocytes in a mouse model of Alzheimer’s disease.Mol. Neurodegener.20241918310.1186/s13024‑024‑00759‑z 39548583
     [Google Scholar]
  85. SasmitaA.O. DeppC. NazarenkoT. Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice.Nat. Neurosci.20242791668167410.1038/s41593‑024‑01730‑3 39103558
     [Google Scholar]
  86. Herculano-HouzelS. The glia/neuron ratio: How it varies uniformly across brain structures and species and what that means for brain physiology and evolution.Glia20146291377139110.1002/glia.22683 24807023
     [Google Scholar]
  87. SaitoT. MatsubaY. MihiraN. Single App knock-in mouse models of Alzheimer’s disease.Nat. Neurosci.201417566166310.1038/nn.3697 24728269
     [Google Scholar]
  88. ZottB. SimonM.M. HongW. A vicious cycle of β amyloid–dependent neuronal hyperactivation.Science2019365645355956510.1126/science.aay0198 31395777
     [Google Scholar]
  89. BuscheM.A. ChenX. HenningH.A. Critical role of soluble amyloid-β for early hippocampal hyperactivity in a mouse model of Alzheimer’s disease.Proc. Natl. Acad. Sci. USA2012109228740874510.1073/pnas.1206171109 22592800
     [Google Scholar]
  90. HarrisS.S. WolfF. De StrooperB. BuscheM.A. Tipping the scales: Peptide-dependent dysregulation of neural circuit dynamics in Alzheimer’s disease.Neuron2020107341743510.1016/j.neuron.2020.06.005 32579881
     [Google Scholar]
  91. HirschfeldL.R. RisacherS.L. NhoK. SaykinA.J. Myelin repair in Alzheimer’s disease: A review of biological pathways and potential therapeutics.Transl. Neurodegener.20221114710.1186/s40035‑022‑00321‑1 36284351
     [Google Scholar]
  92. HuangZ. JordanJ.D. ZhangQ. Myelin pathology in Alzheimer’s disease: Potential therapeutic opportunities.Aging Dis.202415269871310.14336/AD.2023.0628 37548935
     [Google Scholar]
  93. ButtT.H. TobiumeM. ReD.B. KariyaS. Physical exercise counteracts aging-associated white matter demyelination causing cognitive decline.Aging Dis.20241552136214810.14336/AD.2024.0216 38377028
     [Google Scholar]
  94. CuiX. GuoY. FangJ. Donepezil, a drug for Alzheimer’s disease, promotes oligodendrocyte generation and remyelination.Acta Pharmacol. Sin.201940111386139310.1038/s41401‑018‑0206‑4 30918344
     [Google Scholar]
  95. ImamuraO. AraiM. DatekiM. OishiK. TakishimaK. Donepezil‐induced oligodendrocyte differentiation is mediated through estrogen receptors.J. Neurochem.2020155549450710.1111/jnc.14927 31778582
     [Google Scholar]
  96. AbiramanK. PolS.U. O’BaraM.A. Anti-muscarinic adjunct therapy accelerates functional human oligodendrocyte repair.J. Neurosci.20153583676368810.1523/JNEUROSCI.3510‑14.2015 25716865
     [Google Scholar]
  97. ChaseT.N. FarlowM.R. Clarence-SmithK. Donepezil Plus Solifenacin (CPC-201) treatment for Alzheimer’s disease.Neurotherapeutics201714240541610.1007/s13311‑016‑0511‑x 28138837
     [Google Scholar]
  98. ChaoF. ZhangY. ZhangL. Fluoxetine promotes Hippocampal Oligodendrocyte maturation and delays learning and memory decline in APP/PS1 Mice.Front. Aging Neurosci.20211262736210.3389/fnagi.2020.627362 33519426
     [Google Scholar]
  99. ChenS. WangT. YaoJ. BrintonR.D. Allopregnanolone promotes neuronal and oligodendrocyte differentiation in vitro and in vivo: Therapeutic implication for Alzheimer’s disease.Neurotherapeutics20201741813182410.1007/s13311‑020‑00874‑x 32632771
     [Google Scholar]
  100. AlankoV. Gaminde-BlascoA. Quintela-LópezT. 27‐hydroxycholesterol promotes oligodendrocyte maturation: Implications for hypercholesterolemia‐associated brain white matter changes.Glia20237161414142810.1002/glia.24348 36779429
     [Google Scholar]
  101. ZangC. LiuH. JuC. Gardenia jasminoides J. Ellis extract alleviated white matter damage through promoting the differentiation of oligodendrocyte precursor cells via suppressing neuroinflammation.Food Funct.20221342131214110.1039/D1FO02127C 35112688
     [Google Scholar]
  102. QiuD. ZhouS. DonnellyJ. XiaD. ZhaoL. Aerobic exercise attenuates abnormal myelination and oligodendrocyte differentiation in 3xTg-AD mice.Exp. Gerontol.202318211229310.1016/j.exger.2023.112293 37730187
     [Google Scholar]
  103. EguchiK. ShindoT. ItoK. Whole-brain low-intensity pulsed ultrasound therapy markedly improves cognitive dysfunctions in mouse models of dementia - Crucial roles of endothelial nitric oxide synthase.Brain Stimul.201811595997310.1016/j.brs.2018.05.012 29857968
     [Google Scholar]
  104. SevignyJ. ChiaoP. BussièreT. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease.Nature20165377618505610.1038/nature19323 27582220
     [Google Scholar]
  105. TuckerS. MöllerC. TegerstedtK. The murine version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice.J. Alzheimers Dis.201543257558810.3233/JAD‑140741 25096615
     [Google Scholar]
  106. ChatilaZK KimE BerléC BACE1 regulates proliferation and neuronal differentiation of newborn cells in the adult hippocampus in mice.eNeuro201854ENEURO.0067-18.201810.1523/ENEURO.0067‑18.201830079376
     [Google Scholar]
  107. SurC. KostJ. ScottD. BACE inhibition causes rapid, regional, and non-progressive volume reduction in Alzheimer’s disease brain.Brain2020143123816382610.1093/brain/awaa332 33253354
     [Google Scholar]
  108. WesselsA.M. LinesC. SternR.A. Cognitive outcomes in trials of two BACE inhibitors in Alzheimer’s disease.Alzheimers Dement.202016111483149210.1002/alz.12164 33049114
     [Google Scholar]
  109. LeitzkeS. SeidelJ. AhrensB. Influence of Anoctamin-4 and -9 on ADAM10 and ADAM17 sheddase function.Membranes202212212310.3390/membranes12020123 35207044
     [Google Scholar]
  110. Fernández-CalleR. KoningsS.C. Frontiñán-RubioJ. APOE in the bullseye of neurodegenerative diseases: Impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases.Mol. Neurodegener.20221716210.1186/s13024‑022‑00566‑4 36153580
     [Google Scholar]
  111. RaulinA.C. DossS.V. TrottierZ.A. IkezuT.C. BuG. LiuC.C. ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies.Mol. Neurodegener.20221717210.1186/s13024‑022‑00574‑4 36348357
     [Google Scholar]
  112. FuW. ShiD. WestawayD. JhamandasJ.H. Bioenergetic mechanisms in astrocytes may contribute to amyloid plaque deposition and toxicity.J. Biol. Chem.201529020125041251310.1074/jbc.M114.618157 25814669
     [Google Scholar]
  113. NielsenH.M. VeerhuisR. HolmqvistB. JanciauskieneS. Binding and uptake of Aβ1‐42 by primary human astrocytes in vitro.Glia200957997898810.1002/glia.20822 19062178
     [Google Scholar]
  114. JänttiH. SitnikovaV. IshchenkoY. Microglial amyloid beta clearance is driven by PIEZO1 channels.J. Neuroinflammation202219114710.1186/s12974‑022‑02486‑y 35706029
     [Google Scholar]
  115. WangY. UllandT.K. UlrichJ.D. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques.J. Exp. Med.2016213566767510.1084/jem.20151948 27091843
     [Google Scholar]
  116. MironV.E. BoydA. ZhaoJ.W. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination.Nat. Neurosci.20131691211121810.1038/nn.3469 23872599
     [Google Scholar]
  117. LiY. ZhangR. HouX. Microglia activation triggers oligodendrocyte precursor cells apoptosis via HSP60.Mol. Med. Rep.201716160360810.3892/mmr.2017.6673 28586011
     [Google Scholar]
/content/journals/car/10.2174/0115672050401966250625171338
Loading
The Interaction between Oligodendrocytes and Aβ in Alzheimer's Disease
Curr Alzheimer Res 22, 403 (2025); https://doi.org/10.2174/0115672050401966250625171338
/content/journals/car/10.2174/0115672050401966250625171338
/content/journals/car/10.2174/0115672050401966250625171338
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Alzheimer's disease; Aβ; central nervous system (CNS); myelin; neurodegenerative disorder; oligodendrocytes

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