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2000
Volume 25, Issue 2
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by loss of the neurons, excessive accumulation of misfolded Aβ and Tau proteins, and degeneration of neural synapses, primarily occurring in the neocortex and the hippocampus regions of the brain. AD Progression is marked by cognitive deterioration, memory decline, disorientation, and loss of problem-solving skills, as well as language. Due to limited comprehension of the factors contributing to AD and its severity due to neuronal loss, even today, the medications approved by the U.S. Food and Drug Administration (FDA) are not precisely efficient and curative. Stem cells possess great potential in aiding AD due to their self-renewal, proliferation, and differentiation properties. Stem cell therapy can aid by replacing the lost neurons, enhancing neurogenesis, and providing an enriched environment to the pre-existing neural cells. Stem cell therapy has provided us with promising results in regard to the animal AD models, and even pre-clinical studies have shown rather positive results. Cell replacement therapies are potential curative means to treat AD, and there are a number of undergoing human clinical trials to make Stem Cell therapy accessible for AD patients. In this review, we aim to discuss the AD pathophysiology and varied stem cell types and their application.

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2024-09-24
2025-03-15
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References

  1. Alzheimer’s Association. 2023 Alzheimer’s disease facts and figures.Alzheimers Dement.20231941598169510.1002/alz.13016 36918389
    [Google Scholar]
  2. YiannopoulouK.G. PapageorgiouS.G. Current and future treatments for Alzheimer’s disease.Ther. Adv. Neurol. Disord.201361193310.1177/1756285612461679 23277790
    [Google Scholar]
  3. HameedS. FuhJ.L. SenanarongV. Role of fluid biomarkers and PET imaging in early diagnosis and its clinical implication in the management of Alzheimer’s disease.J. Alzheimers Dis. Rep.202041213710.3233/ADR‑190143 32206755
    [Google Scholar]
  4. GrossbergG.T. Cholinesterase inhibitors for the treatment of Alzheimer’s disease: Getting on and staying on.Curr. Ther. Res. Clin. Exp.200364421623510.1016/S0011‑393X(03)00059‑6 24944370
    [Google Scholar]
  5. LukiwW.J. Amyloid beta (Aβ) peptide modulators and other current treatment strategies for Alzheimer’s disease (AD).Expert Opin. Emerg. Drugs2012171436010.1517/14728214.2012.672559 22439907
    [Google Scholar]
  6. Alzheimer’s Association. 2022 Alzheimer’s disease facts and figures.Alzheimers Dement.202218470078910.1002/alz.12638 35289055
    [Google Scholar]
  7. RajmohanR. ReddyP.H. Amyloid-beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer’s disease neurons.J. Alzheimers Dis.201757497599910.3233/JAD‑160612 27567878
    [Google Scholar]
  8. O’BrienR.J. WongP.C. Amyloid precursor protein processing and Alzheimer’s disease.Annu. Rev. Neurosci.201134118520410.1146/annurev‑neuro‑061010‑113613 21456963
    [Google Scholar]
  9. SelkoeD.J. Alzheimer’s disease: Genes, proteins, and therapy.Physiol. Rev.200181274176610.1152/physrev.2001.81.2.741 11274343
    [Google Scholar]
  10. BekrisL.M. YuC.E. BirdT.D. TsuangD.W. Genetics of Alzheimer disease.J. Geriatr. Psychiatry Neurol.201023421322710.1177/0891988710383571 21045163
    [Google Scholar]
  11. MedeirosR. Baglietto-VargasD. LaFerlaF.M. The role of tau in Alzheimer’s disease and related disorders.CNS Neurosci. Ther.201117551452410.1111/j.1755‑5949.2010.00177.x 20553310
    [Google Scholar]
  12. ZhaoJ. FuY. YamazakiY. APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids.Nat. Commun.2020111554010.1038/s41467‑020‑19264‑0 33139712
    [Google Scholar]
  13. LiuC.C. KanekiyoT. XuH. BuG. BuG. Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy.Nat. Rev. Neurol.20139210611810.1038/nrneurol.2012.263 23296339
    [Google Scholar]
  14. PîrşcoveanuD.F.V. Tau protein in neurodegenerative diseases - a review.Rev. Roum. Morphol. Embryol.201758411411150
    [Google Scholar]
  15. Mietelska-PorowskaA. WasikU. GorasM. FilipekA. NiewiadomskaG. Tau protein modifications and interactions: Their role in function and dysfunction.Int. J. Mol. Sci.20141534671471310.3390/ijms15034671 24646911
    [Google Scholar]
  16. SchaefferH.J. WeberM.J. Mitogen-activated protein kinases: Specific messages from ubiquitous messengers.Mol. Cell. Biol.19991942435244410.1128/MCB.19.4.2435 10082509
    [Google Scholar]
  17. RawatP. SeharU. BishtJ. SelmanA. CulbersonJ. ReddyP.H. Phosphorylated tau in Alzheimer’s disease and other tauopathies.Int. J. Mol. Sci.202223211284110.3390/ijms232112841 36361631
    [Google Scholar]
  18. ClarkA.R. OhlmeyerM. Protein phosphatase 2A as a therapeutic target in inflammation and neurodegeneration.Pharmacol. Ther.201920118120110.1016/j.pharmthera.2019.05.016 31158394
    [Google Scholar]
  19. MurphyM.P. LeVineH.III Alzheimer’s disease and the amyloid-β peptide.J. Alzheimers Dis.201019131132310.3233/JAD‑2010‑1221 20061647
    [Google Scholar]
  20. VassarR. KovacsD.M. YanR. WongP.C. The beta-secretase enzyme BACE in health and Alzheimer’s disease: Regulation, cell biology, function, and therapeutic potential.J. Neurosci.20092941127871279410.1523/JNEUROSCI.3657‑09.2009 19828790
    [Google Scholar]
  21. ChowV.W. MattsonM.P. WongP.C. GleichmannM. An overview of APP processing enzymes and products.Neuromolecular Med.201012111210.1007/s12017‑009‑8104‑z 20232515
    [Google Scholar]
  22. YangY.H. HuangL.C. HsiehS.W. HuangL.J. Dynamic blood concentrations of Aβ1–40 and Aβ1–42 in Alzheimer’s disease.Front. Cell Dev. Biol.2020876810.3389/fcell.2020.00768 32850865
    [Google Scholar]
  23. LemereC.A. MasliahE. Can Alzheimer disease be prevented by amyloid-β immunotherapy?Nat. Rev. Neurol.20106210811910.1038/nrneurol.2009.219 20140000
    [Google Scholar]
  24. WalkerL.C. Aβ plaques.Free Neuropathol.2020131110.17879/freeneuropathology‑2020‑3025
    [Google Scholar]
  25. DuboisB. HampelH. FeldmanH.H. Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria.Alzheimers Dement.201612329232310.1016/j.jalz.2016.02.002 27012484
    [Google Scholar]
  26. CataniaM. GiacconeG. SalmonaM. TagliaviniF. Di FedeG. Dreaming of a new world where Alzheimer’s Is a treatable disorder.Front. Aging Neurosci.20191131710.3389/fnagi.2019.00317 31803047
    [Google Scholar]
  27. Pardo-MorenoT. González-AcedoA. Rivas-DomínguezA. Therapeutic approach to Alzheimer’s disease: Current treatments and new perspectives.Pharmaceutics2022146111710.3390/pharmaceutics14061117 35745693
    [Google Scholar]
  28. LiuX.Y. YangL.P. ZhaoL. Stem cell therapy for Alzheimer’s disease.World J. Stem Cells202012878780210.4252/wjsc.v12.i8.787 32952859
    [Google Scholar]
  29. BiehlJ.K. RussellB. Introduction to stem cell therapy.J. Cardiovasc. Nurs.20092429810310.1097/JCN.0b013e318197a6a5 19242274
    [Google Scholar]
  30. LatchneyS.E. EischA.J. Therapeutic application of neural stem cells and adult neurogenesis for neurodegenerative disorders: Regeneration and beyond.Eur. J. Neurodegener. Dis.201213335351 25729743
    [Google Scholar]
  31. Hachimi-IdrissiS. Stem cell therapy in neurological disorders: Promises and concerns.Explor. Neuroprotective Ther.20233534636210.37349/ent.2023.00055
    [Google Scholar]
  32. DuanY. LyuL. ZhanS. Stem cell therapy for Alzheimer’s disease: A scoping review for 2017–2022.Biomedicines202311112010.3390/biomedicines11010120 36672626
    [Google Scholar]
  33. CaoZ. KongF. DingJ. ChenC. HeF. DengW. Promoting Alzheimer’s disease research and therapy with stem cell technology.Stem Cell Res. Ther.202415113610.1186/s13287‑024‑03737‑w 38715083
    [Google Scholar]
  34. RomitoA. CobellisG. Pluripotent stem cells: Current understanding and future directions.Stem Cells Int.201620161945149210.1155/2016/9451492 26798367
    [Google Scholar]
  35. MedvedevS.P. ShevchenkoA.I. ZakianS.M. Induced pluripotent stem cells: Problems and advantages when applying them in regenerative medicine.Acta Nat. (Engl. Ed.)201022182710.32607/20758251‑2010‑2‑2‑18‑27 22649638
    [Google Scholar]
  36. FouadG.I. Stem cells as a promising therapeutic approach for Alzheimer’s disease: A review.Bull. Natl. Res. Cent.20194315210.1186/s42269‑019‑0078‑x
    [Google Scholar]
  37. SachdevaP. JiS. GhoshS. Plausible role of stem cell types for treating and understanding the pathophysiology of depression.Pharmaceutics202315381410.3390/pharmaceutics15030814 36986674
    [Google Scholar]
  38. ZakrzewskiW. DobrzyńskiM. SzymonowiczM. RybakZ. Stem cells: Past, present, and future.Stem Cell Res. Ther.20191016810.1186/s13287‑019‑1165‑5 30808416
    [Google Scholar]
  39. KarvelasN. BennettS. PolitisG. KourisN.I. KoleC. Advances in stem cell therapy in Alzheimer’s disease: A comprehensive clinical trial review.Stem Cell Investig.202292210.21037/sci‑2021‑063 35280344
    [Google Scholar]
  40. YueW. LiY. ZhangT. ESC-derived basal forebrain cholinergic neurons ameliorate the cognitive symptoms associated with Alzheimer’s disease in mouse models.Stem Cell Reports20155577679010.1016/j.stemcr.2015.09.010 26489896
    [Google Scholar]
  41. ChenZ.R. HuangJ.B. YangS.L. HongF.F. Role of cholinergic signaling in Alzheimer’s disease.Molecules2022276181610.3390/molecules27061816 35335180
    [Google Scholar]
  42. LiuA.K.L. ChangR.C.C. PearceR.K.B. GentlemanS.M. Nucleus basalis of Meynert revisited: Anatomy, history and differential involvement in Alzheimer’s and Parkinson’s disease.Acta Neuropathol.2015129452754010.1007/s00401‑015‑1392‑5 25633602
    [Google Scholar]
  43. MartinezJ.L. ZammitM.D. WestN.R. ChristianB.T. BhattacharyyaA. Basal forebrain cholinergic neurons: Linking down syndrome and Alzheimer’s disease.Front. Aging Neurosci.20211370387610.3389/fnagi.2021.703876 34322015
    [Google Scholar]
  44. DibajniaP. MorsheadC.M. Role of neural precursor cells in promoting repair following stroke.Acta Pharmacol. Sin.2013341789010.1038/aps.2012.107 23064725
    [Google Scholar]
  45. VorheesC.V. WilliamsM.T. Morris water maze: Procedures for assessing spatial and related forms of learning and memory.Nat. Protoc.20061284885810.1038/nprot.2006.116 17406317
    [Google Scholar]
  46. LiuY. WeickJ.P. LiuH. Medial ganglionic eminence–like cells derived from human embryonic stem cells correct learning and memory deficits.Nat. Biotechnol.201331544044710.1038/nbt.2565 23604284
    [Google Scholar]
  47. WaldauB. Stem cell transplantation for enhancement of learning and memory in adult neurocognitive disorders.Aging Dis.2010116071
    [Google Scholar]
  48. HerbertsC.A. KwaM.S.G. HermsenH.P.H. Risk factors in the development of stem cell therapy.J. Transl. Med.2011912910.1186/1479‑5876‑9‑29 21418664
    [Google Scholar]
  49. ZhaoX. MooreD.L. Neural stem cells: Developmental mechanisms and disease modeling.Cell Tissue Res.201837111610.1007/s00441‑017‑2738‑1 29196810
    [Google Scholar]
  50. Fontán-LozanoÁ. MorcuendeS. Davis-López de CarrizosaM.A. Benítez-TemiñoB. MejíasR. MatarredonaE.R. To become or not to become tumorigenic: Subventricular zone versus hippocampal neural stem cells.Front. Oncol.20201060221710.3389/fonc.2020.602217 33330101
    [Google Scholar]
  51. LlorenteV. VelardeP. DescoM. Gómez-GaviroM.V. Current understanding of the neural stem cell niches.Cells20221119300210.3390/cells11193002 36230964
    [Google Scholar]
  52. AgerR.R. DavisJ.L. AgazaryanA. Human neural stem cells improve cognition and promote synaptic growth in two complementary transgenic models of Alzheimer’s disease and neuronal loss.Hippocampus201525781382610.1002/hipo.22405 25530343
    [Google Scholar]
  53. ColonnaM. ButovskyO. Microglia function in the central nervous system during health and neurodegeneration.Annu. Rev. Immunol.201735144146810.1146/annurev‑immunol‑051116‑052358 28226226
    [Google Scholar]
  54. MuzioL. ViottiA. MartinoG. Microglia in neuroinflammation and neurodegeneration: from understanding to therapy.Front. Neurosci.20211574206510.3389/fnins.2021.742065 34630027
    [Google Scholar]
  55. HanX. ChenM. WangF. Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice.Cell Stem Cell201312334235310.1016/j.stem.2012.12.015 23472873
    [Google Scholar]
  56. De GioiaR. BiellaF. CitterioG. Neural stem cell transplantation for neurodegenerative diseases.Int. J. Mol. Sci.2020219310310.3390/ijms21093103 32354178
    [Google Scholar]
  57. KaminskaA. RadoszkiewiczK. RybkowskaP. WedzinskaA. SarnowskaA. Interaction of neural stem cells (NSCs) and mesenchymal stem cells (MSCs) as a promising approach in brain study and nerve regeneration.Cells2022119146410.3390/cells11091464 35563770
    [Google Scholar]
  58. SandeliusÅ. PorteliusE. KällénÅ. Elevated CSF GAP‐43 is Alzheimer’s disease specific and associated with tau and amyloid pathology.Alzheimers Dement.2019151556410.1016/j.jalz.2018.08.006 30321501
    [Google Scholar]
  59. GreelyH.T. ChoM.K. HogleL.F. SatzD.M. Thinking about the human neuron mouse.Am. J. Bioeth.200775274010.1080/15265160701290371 17497502
    [Google Scholar]
  60. Pacheco-HerreroM. Soto-RojasL.O. Reyes-SabaterH. Current status and challenges of stem cell treatment for Alzheimer’s disease.J. Alzheimers Dis.202184391793510.3233/JAD‑200863 34633316
    [Google Scholar]
  61. ChanH.J. YanshreeJ. RoyJ. TipoeG.L. FungM.L. LimL.W. Therapeutic potential of human stem cell implantation in Alzheimer’s disease.Int. J. Mol. Sci.202122181015110.3390/ijms221810151 34576314
    [Google Scholar]
  62. BaluD. Valencia-OlveraA.C. NguyenA. A small-molecule TLR4 antagonist reduced neuroinflammation in female E4FAD mice.Alzheimers Res. Ther.202315118110.1186/s13195‑023‑01330‑6 37858252
    [Google Scholar]
  63. WangC.Y. LinH.C. SongY.P. Protein kinase C-dependent growth-associated protein 43 phosphorylation regulates gephyrin aggregation at developing GABAergic synapses.Mol. Cell. Biol.201535101712172610.1128/MCB.01332‑14 25755278
    [Google Scholar]
  64. HayashiY. LinH.T. LeeC.C. TsaiK.J. Effects of neural stem cell transplantation in Alzheimer’s disease models.J. Biomed. Sci.20202712910.1186/s12929‑020‑0622‑x 31987051
    [Google Scholar]
  65. WeissM.L. TroyerD.L. Stem cells in the umbilical cord.Stem Cell Rev.20062215516210.1007/s12015‑006‑0022‑y 17237554
    [Google Scholar]
  66. HmadchaA. Martin-MontalvoA. GauthierB.R. SoriaB. Capilla-GonzalezV. Therapeutic potential of mesenchymal stem cells for cancer therapy.Front. Bioeng. Biotechnol.202084310.3389/fbioe.2020.00043 32117924
    [Google Scholar]
  67. KangH-J. Mesenchymal stem cell-derived exosomes regulate microglia phenotypes: A promising treatment for acute central nervous system injury.Neural Regen. Res.20221881657166510.4103/1673‑5374.363819
    [Google Scholar]
  68. HanD. ZhengX. WangX. JinT. CuiL. ChenZ. Mesenchymal stem/stromal cell-mediated mitochondrial transfer and the therapeutic potential in treatment of neurological diseases.Stem Cells Int.2020202011610.1155/2020/8838046 32724315
    [Google Scholar]
  69. KanyS. VollrathJ.T. ReljaB. Cytokines in inflammatory disease.Int. J. Mol. Sci.20192023600810.3390/ijms20236008 31795299
    [Google Scholar]
  70. QinC. WangK. ZhangL. BaiL. Stem cell therapy for Alzheimer’s disease: An overview of experimental models and reality.Animal Model. Exp. Med.202251152610.1002/ame2.12207 35229995
    [Google Scholar]
  71. KimH.S. LeeJ.H. RohK.H. JunH.J. KangK.S. KimT.Y. Clinical trial of human umbilical cord blood-derived stem cells for the treatment of moderate-to-severe atopic dermatitis: Phase I/IIa studies.Stem Cells201735124825510.1002/stem.2401 27256706
    [Google Scholar]
  72. JiangK ZhuY ZhangL New prospects for stem cell therapy in Alzheimer’s disease.Hippocampus - cytoarchitecture and diseases. London: InTechOpen2021
    [Google Scholar]
  73. KimH.J. SeoS.W. ChangJ.W. Stereotactic brain injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: A phase 1 clinical trial.Alzheimers Dement. (N. Y.)2015129510210.1016/j.trci.2015.06.007 29854930
    [Google Scholar]
  74. ZhangG. LiY. ReussJ.L. Stable intracerebral transplantation of neural stem cells for the treatment of paralysis due to ischemic stroke.Stem Cells Transl. Med.2019810999100710.1002/sctm.18‑0220 31241246
    [Google Scholar]
  75. KueperJ.K. SpeechleyM. Montero-OdassoM. The Alzheimer’s disease assessment scale–cognitive subscale (ADAS-Cog): Modifications and responsiveness in pre-dementia populations. A Narrative Review.J. Alzheimers Dis.201863242344410.3233/JAD‑170991 29660938
    [Google Scholar]
  76. HrishiA.P. SethuramanM. Cere brospinal fluid (CSF) analysis and interpretation in neurocritical care for acute neurological conditions.Indian J. Crit. Care Med.201923Suppl. 2S115S11910.5005/jp‑journals‑10071‑23187
    [Google Scholar]
  77. PredaM.B. NeculachiC.A. FenyoI.M. Short lifespan of syngeneic transplanted MSC is a consequence of in vivo apoptosis and immune cell recruitment in mice.Cell Death Dis.202112656610.1038/s41419‑021‑03839‑w 34075029
    [Google Scholar]
  78. BartolucciJ. VerdugoF.J. GonzálezP.L. Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure.Circ. Res.2017121101192120410.1161/CIRCRESAHA.117.310712 28974553
    [Google Scholar]
  79. GriffethL.K. Use of PET/CT scanning in cancer patients: Technical and practical considerations.Proc. Bayl. Univ. Med. Cent.200518432133010.1080/08998280.2005.11928089 16252023
    [Google Scholar]
  80. MarcusC. MenaE. SubramaniamR.M. Brain PET in the diagnosis of Alzheimer’s disease.Clin. Nucl. Med.20143910e413e42610.1097/RLU.0000000000000547 25199063
    [Google Scholar]
  81. SasakiS. HorieY. The effects of an uninterrupted switch from donepezil to galantamine without dose titration on behavioral and psychological symptoms of dementia in Alzheimer’s disease.Dement. Geriatr. Cogn. Disord. Extra20144213113910.1159/000362871 24987402
    [Google Scholar]
  82. WankhadeU.D. ShenM. KolheR. FulzeleS. Advances in adipose‐derived stem cells isolation, characterization, and application in regenerative tissue engineering.Stem Cells Int.201620161320680710.1155/2016/3206807 26981130
    [Google Scholar]
  83. PatelA.B. TiwariV. VeeraiahP. SabaK. Increased astroglial activity and reduced neuronal function across brain in AβPP-PS1 mouse model of Alzheimer’s disease.J. Cereb. Blood Flow Metab.20183871213122610.1177/0271678X17709463 28585882
    [Google Scholar]
  84. NaeimiA. ZaminyA. AminiN. BalabandiR. GolipoorZ. Effects of melatonin-pretreated adipose-derived mesenchymal stem cells (MSC) in an animal model of spinal cord injury.BMC Neurosci.20222316510.1186/s12868‑022‑00752‑6 36384473
    [Google Scholar]
  85. ShenZ. HuangW. LiuJ. TianJ. WangS. RuiK. Effects of mesenchymal stem cell-derived exosomes on autoimmune diseases.Front. Immunol.20211274919210.3389/fimmu.2021.749192 34646275
    [Google Scholar]
  86. LongC. WangJ. GanW. QinX. YangR. ChenX. Therapeutic potential of exosomes from adipose-derived stem cells in chronic wound healing.Front. Surg.20229103028810.3389/fsurg.2022.1030288 36248361
    [Google Scholar]
  87. LiangT. WuZ. LiJ. WuS. ShiW. WangL. The emerging double-edged sword role of exosomes in Alzheimer’s disease.Front. Aging Neurosci.202315120911510.3389/fnagi.2023.1209115 37396664
    [Google Scholar]
  88. Madani NeishabooriA. EshraghiA. Tasouji AslA. ShariatpanahiM. YousefifardM. GorjiA. Adipose tissue‐derived stem cells as a potential candidate in treatment of Alzheimer’s disease: A systematic review on preclinical studies.Pharmacol. Res. Perspect.2022104e0097710.1002/prp2.977 35718918
    [Google Scholar]
  89. MuthuS. BapatA. JainR. JeyaramanN. JeyaramanM. Exosomal therapy—a new frontier in regenerative medicine.Stem Cell Investig.202187710.21037/sci‑2020‑037 33969112
    [Google Scholar]
  90. TsujiW. RubinJ.P. MarraK.G. Adipose-derived stem cells: Implications in tissue regeneration.World J. Stem Cells20146331232110.4252/wjsc.v6.i3.312 25126381
    [Google Scholar]
  91. NakanoM. KubotaK. KobayashiE. Bone marrow-derived mesenchymal stem cells improve cognitive impairment in an Alzheimer’s disease model by increasing the expression of microRNA-146a in hippocampus.Sci. Rep.20201011077210.1038/s41598‑020‑67460‑1 32612165
    [Google Scholar]
  92. HaugheyN.J. LiuD. NathA. BorchardA.C. MattsonM.P. Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid β-peptideby amyloid β-peptide.Neuromolecular Med.20021212513610.1385/NMM:1:2:125 12025858
    [Google Scholar]
  93. MuckeL. SelkoeD.J. Neurotoxicity of amyloid β-protein: Synaptic and network dysfunction.Cold Spring Harb. Perspect. Med.201227a006338a810.1101/cshperspect.a006338 22762015
    [Google Scholar]
  94. López-GonzálezI. SchlüterA. AsoE. Neuroinflammatory signals in Alzheimer disease and APP/PS1 transgenic mice: Correlations with plaques, tangles, and oligomeric species.J. Neuropathol. Exp. Neurol.201574431934410.1097/NEN.0000000000000176 25756590
    [Google Scholar]
  95. RegmiS. LiuD.D. ShenM. Mesenchymal stromal cells for the treatment of Alzheimer’s disease: Strategies and limitations.Front. Mol. Neurosci.202215101122510.3389/fnmol.2022.1011225 36277497
    [Google Scholar]
  96. HernándezA.E. GarcíaE. Mesenchymal stem cell therapy for Alzheimer’s disease.Stem Cells Int.2021202111210.1155/2021/7834421 34512767
    [Google Scholar]
  97. FanW. LiangC. OuM. MicroRNA-146a is a wide-reaching neuroinflammatory regulator and potential treatment target in neurological diseases.Front. Mol. Neurosci.2020139010.3389/fnmol.2020.00090 32581706
    [Google Scholar]
  98. NevesA.F. CamargoC. PremerC. HareJ.M. BaumelB.S. PintoM. Intravenous administration of mesenchymal stem cells reduces Tau phosphorylation and inflammation in the 3xTg-AD mouse model of Alzheimer’s disease.Exp. Neurol.2021341Mar11370610.1016/j.expneurol.2021.113706 33757765
    [Google Scholar]
  99. QinC. LuY. WangK. Transplantation of bone marrow mesenchymal stem cells improves cognitive deficits and alleviates neuropathology in animal models of Alzheimer’s disease: A meta-analytic review on potential mechanisms.Transl. Neurodegener.2020912010.1186/s40035‑020‑00199‑x 32460886
    [Google Scholar]
  100. OuryazdanpanahN. DabiriS. DerakhshaniA. VahidiR. FarsinejadA. Peripheral blood-derived mesenchymal stem cells: Growth factor-free isolation, molecular characterization and differentiation.Iran. J. Pathol.2018134461466 30774686
    [Google Scholar]
  101. PetraliaM.C. BattagliaG. BrunoV. The role of macrophage migration inhibitory factor in Alzheimer′s disease: Conventionally pathogenetic or unconventionally protective?Molecules202025229110.3390/molecules25020291 31936865
    [Google Scholar]
  102. WuC.C. WangI.F. ChiangP.M. WangL.C. ShenC.K.J. TsaiK.J. G-CSF-mobilized bone marrow mesenchymal stem cells replenish neural lineages in Alzheimer’s disease mice via CXCR4/SDF-1 chemotaxis.Mol. Neurobiol.20175486198621210.1007/s12035‑016‑0122‑x 27709493
    [Google Scholar]
  103. KumarM.A. BabaS.K. SadidaH.Q. Extracellular vesicles as tools and targets in therapy for diseases.Signal Transduct. Target. Ther.2024912710.1038/s41392‑024‑01735‑1 38311623
    [Google Scholar]
  104. GuoM. YinZ. ChenF. LeiP. Mesenchymal stem cell-derived exosome: A promising alternative in the therapy of Alzheimer’s disease.Alzheimers Res. Ther.202012110910.1186/s13195‑020‑00670‑x 32928293
    [Google Scholar]
  105. SurotoH. AsrielA. De VegaB. SamijoS.K. Early and late apoptosis protein expression (Bcl-2, BAX and p53) in traumatic brachial plexus injury.J. Musculoskelet. Neuronal Interact.2021214528532
    [Google Scholar]
  106. TakahashiK. YamanakaS. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell2006126466367610.1016/j.cell.2006.07.024 16904174
    [Google Scholar]
  107. YeL. SwingenC. ZhangJ. Induced pluripotent stem cells and their potential for basic and clinical sciences.Curr. Cardiol. Rev.201391637210.2174/157340313805076278 22935022
    [Google Scholar]
  108. LiL. ChaoJ. ShiY. Modeling neurological diseases using iPSC-derived neural cells.Cell Tissue Res.2018371114315110.1007/s00441‑017‑2713‑x 29079884
    [Google Scholar]
  109. ArmijoE. EdwardsG. FloresA. Induced pluripotent stem cell-derived neural precursors improve memory, synaptic and pathological abnormalities in a mouse model of Alzheimer’s disease.Cells2021107180210.3390/cells10071802 34359972
    [Google Scholar]
  110. SaundersA. GrangerA.J. SabatiniB.L. Corelease of acetylcholine and GABA from cholinergic forebrain neurons.eLife20154e0641210.7554/eLife.06412 25723967
    [Google Scholar]
  111. TapellaL DematteisG GenazzaniA De PaolaM LimD Immortalized hippocampal astrocytes from 3xTg-AD mice, a new model to study disease-related astrocytic dysfunction: A comparative review.Neural Regen Res2023188010.4103/1673‑5374.363192 36751778
    [Google Scholar]
  112. MajoloF. MarinowicD.R. MachadoD.C. Da CostaJ.C. Important advances in Alzheimer’s disease from the use of induced pluripotent stem cells.J. Biomed. Sci.20192611510.1186/s12929‑019‑0501‑5 30728025
    [Google Scholar]
  113. ZayedM.A. SultanS. AlsaabH.O. Stem-cell-based therapy: The celestial weapon against neurological disorders.Cells20221121347610.3390/cells11213476 36359871
    [Google Scholar]
  114. FordE. PearlmanJ. RuanT. Human pluripotent stem cells-based therapies for neurodegenerative diseases: current status and challenges.Cells2020911251710.3390/cells9112517 33233861
    [Google Scholar]
  115. AlyR.M. Current state of stem cell-based therapies: An overview.Stem Cell Investig.2020788810.21037/sci‑2020‑001 32695801
    [Google Scholar]
  116. ChenX. JiangS. WangR. BaoX. Neural stem cells in the treatment of Alzheimer’s disease: current status, challenges, and future prospects.J. Alzheimers Dis.2022Nov11410.3233/JAD‑220721 36336934
    [Google Scholar]
  117. GoldbergJ.S. HirschiK.K. Diverse roles of the vasculature within the neural stem cell niche.Regen. Med.20094687989710.2217/rme.09.61 19903006
    [Google Scholar]
  118. GuoW. ZhangX. ZhaiJ. XueJ. The roles and applications of neural stem cells in spinal cord injury repair.Front. Bioeng. Biotechnol.20221096686610.3389/fbioe.2022.966866 36105599
    [Google Scholar]
  119. HoangD.M. PhamP.T. BachT.Q. Stem cell-based therapy for human diseases.Signal Transduct. Target. Ther.20227127210.1038/s41392‑022‑01134‑4 35933430
    [Google Scholar]
  120. RockensteinE. Neuropeptide treatment with cerebrolysin enhances the survival of grafted neural stem cell in an α-synuclein transgenic model of Parkinson’s disease.J. Exp. Neurosci.20169Suppl. 213114010.4137/JEN.S25521
    [Google Scholar]
  121. MirandaM. MoriciJ.F. ZanoniM.B. BekinschteinP. Brain-derived neurotrophic factor: A key molecule for memory in the healthy and the pathological brain.Front. Cell. Neurosci.20191336336310.3389/fncel.2019.00363 31440144
    [Google Scholar]
  122. WaldauB. ShettyA.K. Behavior of neural stem cells in the Alzheimer brain.Cell. Mol. Life Sci.200865152372238410.1007/s00018‑008‑8053‑y 18500448
    [Google Scholar]
  123. KimH LeeS ChangJW KimA JangH NaDL Intraspinal cavity injection of human mesenchymal stem cells and tracking their migration into the rat brain.J Vis Exp202116810.3791/62120 33616092
    [Google Scholar]
  124. ŠpanićE. Langer HorvatL. HofP.R. ŠimićG. Role of microglial cells in Alzheimer’s disease tau propagation.Front. Aging Neurosci.20191127110.3389/fnagi.2019.00271 31636558
    [Google Scholar]
  125. MaK. FoxL. ShiG. Generation of neural stem cell-like cells from bone marrow-derived human mesenchymal stem cells.Neurol. Res.201133101083109310.1179/1743132811Y.0000000053 22196762
    [Google Scholar]
  126. ChenG. XuT. YanY. Amyloid beta: Structure, biology and structure-based therapeutic development.Acta Pharmacol. Sin.20173891205123510.1038/aps.2017.28 28713158
    [Google Scholar]
  127. HickmanS. IzzyS. SenP. MorsettL. El KhouryJ. Microglia in neurodegeneration.Nat. Neurosci.201821101359136910.1038/s41593‑018‑0242‑x 30258234
    [Google Scholar]
  128. LohQ.L. ChoongC. Three-dimensional scaffolds for tissue engineering applications: Role of porosity and pore size.Tissue Eng. Part B Rev.201319648550210.1089/ten.teb.2012.0437 23672709
    [Google Scholar]
  129. HuaY. DaiX. XuY. Drug repositioning: Progress and challenges in drug discovery for various diseases.Eur. J. Med. Chem.2022234Feb11423910.1016/j.ejmech.2022.114239 35290843
    [Google Scholar]
  130. CummingsJ. LeeG. NahedP. Alzheimer’s disease drug development pipeline: 2022.Alzheimers Dement. (N. Y.)202281e1229510.1002/trc2.12295 35516416
    [Google Scholar]
  131. de VruehR.L.A. CrommelinD.J.A. Reflections on the future of pharmaceutical public-private partnerships: From input to impact.Pharm. Res.201734101985199910.1007/s11095‑017‑2192‑5 28589444
    [Google Scholar]
  132. YiannopoulouK.G. PapageorgiouS.G. Current and future treatments in Alzheimer disease: An update.J. Cent. Nerv. Syst. Dis.202012110.1177/1179573520907397 32165850
    [Google Scholar]
  133. LiuJ. ChangL. SongY. LiH. WuY. The role of NMDA receptors in Alzheimer’s disease.Front. Neurosci.201913434310.3389/fnins.2019.00043 30800052
    [Google Scholar]
  134. TariotP.N. FarlowM.R. GrossbergG.T. GrahamS.M. McDonaldS. GergelI. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: A randomized controlled trial.JAMA2004291331732410.1001/jama.291.3.317 14734594
    [Google Scholar]
  135. CummingsJ. LeeG. ZhongK. FonsecaJ. TaghvaK. Alzheimer’s disease drug development pipeline: 2021.Alzheimers Dement. (N. Y.)202171e1217910.1002/trc2.12179 34095440
    [Google Scholar]
  136. FilippiniG. Del GiovaneC. ClericoM. Treatment with disease-modifying drugs for people with a first clinical attack suggestive of multiple sclerosis.Cochrane Libr.201720174CD01220010.1002/14651858.CD012200.pub2 28440858
    [Google Scholar]
  137. TongL.M. FongH. HuangY. Stem cell therapy for Alzheimer’s disease and related disorders: Current status and future perspectives.Exp. Mol. Med.2015473e151110.1038/emm.2014.124 25766620
    [Google Scholar]
  138. TompkinsB.A. DiFedeD.L. KhanA. Allogeneic mesenchymal stem cells ameliorate aging frailty: A phase II randomized, double-blind, placebo-controlled clinical trial.J. Gerontol. A Biol. Sci. Med. Sci.201772111513152210.1093/gerona/glx137 28977399
    [Google Scholar]
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