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2000
Volume 20, Issue 5
  • ISSN: 1574-8855
  • E-ISSN: 2212-3903

Abstract

Alzheimer's disease is a neurological condition that is becoming increasingly common and is typified by dementia. Drug development for AD is a major issue with a startlingly high failure rate despite a marked increase in the frequency of the disease linked to genetic factors. As AD is the most common neurological illness and contributes to both the high patient burden and the cost of healthcare, this issue must be addressed.

The current manuscript aims to focus on the current treatment approaches of newer drugs under clinical trials of Alzheimer’s disease by targeting the various pathological pathways that are involved in AD.

Data provided in this review are from literature surveys and ongoing clinical trials from reputed search engines like PubMed, ResearchGate, Science Direct, and Google Scholar, as well as from various respected authors and—registered websites such as memory.ucsf.edu/genetics/familial-Alzheimer’s-disease and https://www.clinicaltrials.gov.

There are diverse forms of drugs and multiple pathways on which many advancements and clinical trials have been conductedand are undergoing. Various investigations and studies are going on.

There are different pathogenesis of AD, such as Tau, vascular, Amyloid β, estrogen deficiency, and the role of gut microbiota in AD. Donepezil, Rivastigmine, ., are currently used for treatment, and certain drugs are in different stages of clinical trials, such as ANI792, ACC-001, CAD106 &ABvac40, and it is concluded that after successful trials of the new drugs, they can be used for the treatment of AD with maximum benefits and less side effect.

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References

  1. ŠkudarL.V. DobrotaD.V. ŠimićG. Common pathogenetic factors in metabolic syndrome and dementia Rad Hrvat.Academies Znan Art Mat Znan202255360-617483
     [Google Scholar]
  2. CuiL. HouN.N. WuH.M. Prevalence of Alzheimer’s disease and Parkinson’s disease in China: An updated systematical analysis.Front. Aging Neurosci.20201260385410.3389/fnagi.2020.603854 33424580
     [Google Scholar]
  3. LeeJ. MeijerE. LangaK.M. Prevalence of dementia in India: National and state estimates from a nationwide study.Alzheimers Dement.20231972898291210.1002/alz.12928 36637034
     [Google Scholar]
  4. AssociationA.S. Alzheimers. Dement.2023Available from: https://www.alz.org/alzheimers-dementia/facts-figures (cited on: 19 Oct, 2023).
  5. ScheltensP. De StrooperB. KivipeltoM. Alzheimer’s disease.Lancet2021397102841577159010.1016/S0140‑6736(20)32205‑4 33667416
     [Google Scholar]
  6. MurdockM.H. TsaiL.H. Insights into Alzheimer’s disease from single-cell genomic approaches.Nat. Neurosci.202326218119510.1038/s41593‑022‑01222‑2 36593328
     [Google Scholar]
  7. ZhaoY. DangM. ZhangW. Neuroprotective effects of Syringic acid against aluminium chloride induced oxidative stress mediated neuroinflammation in rat model of Alzheimer’s disease.J. Funct. Foods20207110400910.1016/j.jff.2020.104009
     [Google Scholar]
  8. KhalafN.E.A. El BannaF.M. YoussefM.Y. MosaadY.M. DabaM.H.Y. AshourR.H. Clopidogrel combats neuroinflammation and enhances learning behavior and memory in a rat model of Alzheimer’s disease.Pharmacol. Biochem. Behav.202019517295610.1016/j.pbb.2020.172956 32474163
     [Google Scholar]
  9. GuerreroA.J. BalmasedaS.A. AguilarJ.P. Alzheimer’s Disease: An Updated Overview of Its Genetics.Int. J. Mol. Sci.2023244375410.3390/ijms24043754 36835161
     [Google Scholar]
  10. JiaoB. LiuH. GuoL. The role of genetics in neurodegenerative dementia: A large cohort study in South China.NPJ Genom. Med.2021616910.1038/s41525‑021‑00235‑3 34389718
     [Google Scholar]
  11. Familial Alzheimer’s Disease2023Available from: https://memory.ucsf.edu/genetics/familial-alzheimer-disease (cited on: Dec 1, 2023).
  12. QuanM. CaoS. WangQ. WangS. JiaJ. Genetic Phenotypes of Alzheimer’s Disease: Mechanisms and Potential Therapy.Phenomics202334333349
     [Google Scholar]
  13. BekrisL.M. YuC.E. BirdT.D. TsuangD.W. Genetics of Alzheimer disease.J. Geriatr. Psychiatry Neurol.201023421322710.1177/0891988710383571 21045163
     [Google Scholar]
  14. JiaL. FuY. ShenL. PSEN1, PSEN2, and APP mutations in 404 Chinese pedigrees with familial Alzheimer’s disease.Alzheimers Dement.202016117819110.1002/alz.12005 31914229
     [Google Scholar]
  15. GoldmanJ.S. HahnS.E. CataniaJ.W. Genetic counseling and testing for Alzheimer disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors.Genet. Med.201113659760510.1097/GIM.0b013e31821d69b8 21577118
     [Google Scholar]
  16. KhalilY.A. RabèsJ.P. BoileauC. VarretM. APOE gene variants in primary dyslipidemia.Atherosclerosis2021328112210.1016/j.atherosclerosis.2021.05.007 34058468
     [Google Scholar]
  17. ZhaoN. RenY. YamazakiY. Alzheimer’s risk factors age, APOE genotype, and sex drive distinct molecular pathways.Neuron20201065727742.e610.1016/j.neuron.2020.02.034 32199103
     [Google Scholar]
  18. BenedetA.L. AlomàM.M. VrillonA. Differences between plasma and cerebrospinal fluid glial fibrillary acidic protein levels across the Alzheimer disease continuum.JAMA Neurol.202178121471148310.1001/jamaneurol.2021.3671 34661615
     [Google Scholar]
  19. PereiraJ.B. JanelidzeS. SmithR. Plasma GFAP is an early marker of amyloid-β but not tau pathology in Alzheimer’s disease.Brain2021144113505351610.1093/brain/awab223 34259835
     [Google Scholar]
  20. PlancheV. BouteloupV. PellegrinI. Validity and performance of blood biomarkers for alzheimer disease to predict dementia risk in a large clinic-based cohort.Neurology20231005e473e48410.1212/WNL.0000000000201479 36261295
     [Google Scholar]
  21. TeunissenC.E. VerberkI.M.W. ThijssenE.H. Blood-based biomarkers for Alzheimer’s disease: Towards clinical implementation.Lancet Neurol.2022211667710.1016/S1474‑4422(21)00361‑6 34838239
     [Google Scholar]
  22. SeinoY. NakamuraT. KawarabayashiT. Cerebrospinal fluid and plasma biomarkers in neurodegenerative diseases.J. Alzheimers Dis.201968139540410.3233/JAD‑181152 30814356
     [Google Scholar]
  23. ZetterbergH. Blood-based biomarkers for Alzheimer’s disease—An update.J. Neurosci. Methods20193192610.1016/j.jneumeth.2018.10.025 30352211
     [Google Scholar]
  24. NabersA. HafermannH. WiltfangJ. GerwertK. Aβ and tau structure‐based biomarkers for a blood‐ and CSF‐based two‐step recruitment strategy to identify patients with dementia due to Alzheimer’s disease.Alzheimers Dement.201911125726310.1016/j.dadm.2019.01.008 30911600
     [Google Scholar]
  25. GobomJ. BenedetA.L. CarlgrenM.N. Antibody-free measurement of cerebrospinal fluid tau phosphorylation across the Alzheimer’s disease continuum.Mol. Neurodegener.20221718110.1186/s13024‑022‑00586‑0 36510321
     [Google Scholar]
  26. JonaitisE.M. JanelidzeS. CodyK.A. Plasma phosphorylated tau 217 in preclinical Alzheimer’s disease.Brain Commun.202352fcad05710.1093/braincomms/fcad057 37013174
     [Google Scholar]
  27. PalmqvistS. JanelidzeS. QuirozY.T. Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders.JAMA2020324877278110.1001/jama.2020.12134 32722745
     [Google Scholar]
  28. ThijssenE.H. La JoieR. StromA. Association of Plasma P-tau217 and P-tau181 with clinical phenotype, neuropathology, and imaging markers in Alzheimer’s disease and frontotemporal lobar degeneration: A retrospective diagnostic performance study.Lancet Neurol.202120973910.1016/S1474‑4422(21)00214‑3 34418401
     [Google Scholar]
  29. MorrisonM.S. AparicioH.J. BlennowK. Ante-mortem plasma phosphorylated tau (181) predicts Alzheimer’s disease neuropathology and regional tau at autopsy.Brain2022145103546355710.1093/brain/awac175 35554506
     [Google Scholar]
  30. ForteaJ. VilaplanaE. IraguiC.M. Clinical and biomarker changes of Alzheimer’s disease in adults with Down syndrome: A cross-sectional study.Lancet2020395102421988199710.1016/S0140‑6736(20)30689‑9 32593336
     [Google Scholar]
  31. ForteaJ. IraguiC.M. BenejamB. Plasma and CSF biomarkers for the diagnosis of Alzheimer’s disease in adults with Down syndrome: A cross-sectional study.Lancet Neurol.2018171086086910.1016/S1474‑4422(18)30285‑0 30172624
     [Google Scholar]
  32. VrillonA. LigerM.F. MartinetM. Plasma neuregulin 1 as a synaptic biomarker in Alzheimer’s disease.Alzheimers Dement.202319S2e06090710.1002/alz.060907
     [Google Scholar]
  33. RibaričS. Detecting Early Cognitive Decline in Alzheimer’s Disease with Brain Synaptic Structural and Functional Evaluation.Biomedicines202311235510.3390/biomedicines11020355 36830892
     [Google Scholar]
  34. QiangQ. HillS.L. ToyotaT. WeiW. AdachiH. CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer’s disease.Sci. Rep.20221211739210.1038/s41598‑022‑20324‑2 36253408
     [Google Scholar]
  35. HawksworthJ. FernándezE. GevaertK. A new generation of AD biomarkers: 2019 to 2021.Ageing Res. Rev.20227910165410.1016/j.arr.2022.101654 35636691
     [Google Scholar]
  36. Van HulleC. JonaitisE.M. BetthauserT.J. An examination of a novel multipanel of CSF biomarkers in the Alzheimer’s disease clinical and pathological continuum.Alzheimers Dement.202117343144510.1002/alz.12204 33336877
     [Google Scholar]
  37. ChenG. XuT. YanY. Amyloid beta: Structure, biology and structure-based therapeutic development.Acta Pharmacol. Sin.20173891205123510.1038/aps.2017.28 28713158
     [Google Scholar]
  38. ZhouR. YangG. ShiY. Macromolecular complex in recognition and proteolysis of amyloid precursor protein in Alzheimer’s disease.Curr. Opin. Struct. Biol.2020611810.1016/j.sbi.2019.09.004 31629221
     [Google Scholar]
  39. KakudaN. MiyasakaT. IwasakiN. Distinct deposition of amyloid-β species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry.Acta Neuropathol. Commun.2017517310.1186/s40478‑017‑0477‑x 29037261
     [Google Scholar]
  40. AguayoL.G. RoaJ.P. BurgosC.F. SanmiguelG.J. Involvement of cholesterol and β-amyloid in the initiation and progression of Alzheimer’s disease.In: Cholesterol.Academic Press2022715745
     [Google Scholar]
  41. KnuppA. MishraS. MartinezR. Depletion of the AD risk gene SORL1 selectively impairs neuronal endosomal traffic independent of amyloidogenic APP processing.Cell Rep.202031910771910.1016/j.celrep.2020.107719 32492427
     [Google Scholar]
  42. TambiniM.D. NorrisK.A. D’AdamioL. Opposite changes in APP processing and human Aβ levels in rats carrying either a protective or a pathogenic APP mutation.eLife20209e5261210.7554/eLife.52612 32022689
     [Google Scholar]
  43. HurJ.Y. γ-Secretase in Alzheimer’s disease.Exp. Mol. Med.202254443344610.1038/s12276‑022‑00754‑8 35396575
     [Google Scholar]
  44. CheclerF. AframE. PiquardP.R. LauritzenI. Is γ-secretase a beneficial inactivating enzyme of the toxic APP C-terminal fragment C99?J. Biol. Chem.202129610048910.1016/j.jbc.2021.100489 33662398
     [Google Scholar]
  45. DhamiM. RajK. SinghS. Neuroprotective effect of fucoxanthin against intracerebroventricular streptozotocin (ICV-STZ) induced cognitive impairment in experimental rats.Curr. Alzheimer Res.202118862363710.2174/1567205018666211118144602 34792011
     [Google Scholar]
  46. KaurS. RajK. GuptaY.K. SinghS. Allicin ameliorates aluminium- and copper-induced cognitive dysfunction in Wistar rats: Relevance to neuro-inflammation, neurotransmitters and Aβ(1–42) analysis.J. Biol. Inorg. Chem.202126449551010.1007/s00775‑021‑01866‑8 34023945
     [Google Scholar]
  47. MuralidarS. AmbiS.V. SekaranS. ThirumalaiD. PalaniappanB. Role of tau protein in Alzheimer’s disease: The prime pathological player.Int. J. Biol. Macromol.20201631599161710.1016/j.ijbiomac.2020.07.327 32784025
     [Google Scholar]
  48. TabeshmehrP. EftekharpourE. Tau; One Protein, So Many Diseases.Biology202312224410.3390/biology12020244 36829521
     [Google Scholar]
  49. GoodsonH.V. JonassonE.M. Microtubules and microtubule-associated proteins.Cold Spring Harb. Perspect. Biol.2018106a02260810.1101/cshperspect.a022608 29858272
     [Google Scholar]
  50. KirschnerM. The discovery of tau protein.Cytoskeleton20231817882 37823566
     [Google Scholar]
  51. CorsiA. BombieriC. ValentiM.T. RomanelliM.G. Tau isoforms: Gaining Insight into MAPT alternative splicing.Int. J. Mol. Sci.202223231538310.3390/ijms232315383 36499709
     [Google Scholar]
  52. ChenX. ChenM. SchaferN.P. WolynesP.G. Exploring the interplay between fibrillization and amorphous aggregation channels on the energy landscapes of tau repeat isoforms.Proc. Natl. Acad. Sci.202011784125413010.1073/pnas.1921702117 32029593
     [Google Scholar]
  53. HolperS. WatsonR. YassiN. Tau as a Biomarker of Neurodegeneration.Int. J. Mol. Sci.20222313730710.3390/ijms23137307 35806324
     [Google Scholar]
  54. WangY. MandelkowE. Tau in physiology and pathology.Nat. Rev. Neurosci.2016171223510.1038/nrn.2015.1 26631930
     [Google Scholar]
  55. GoedertM. SpillantiniM.G. Ordered assembly of tau protein and neurodegeneration.Tau Biology201932110.1007/978‑981‑32‑9358‑8_1
     [Google Scholar]
  56. AlmansoubH.A.M.M. TangH. WuY. Tau abnormalities and the potential therapy in Alzheimer’s disease.J. Alzheimers Dis.2019671133310.3233/JAD‑180868 30507581
     [Google Scholar]
  57. ChuD. LiuF. Pathological changes of tau related to Alzheimer’s disease.ACS Chem. Neurosci.201910293194410.1021/acschemneuro.8b00457 30346708
     [Google Scholar]
  58. MelkováK. ZapletalV. NarasimhanS. Structure and functions of microtubule associated proteins tau and MAP2c: Similarities and differences.Biomolecules20199310510.3390/biom9030105 30884818
     [Google Scholar]
  59. OksmanI. Alzheimer’s disease: Integrating neuroscience data into computational models for understanding impaired synaptic plasticity in the hippocampus.Lithuanian University Health Sci Res Manag Sys201991
     [Google Scholar]
  60. LaurettiE. PraticòD. Alzheimer’s disease: Phenotypic approaches using disease models and the targeting of tau protein.Expert Opin. Ther. Pat.20202443190
     [Google Scholar]
  61. ApetriA. CrespoR. JuraszekJ. A common antigenic motif recognized by naturally occurring human VH5–51/VL4–1 anti-tau antibodies with distinct functionalities.Acta Neuropathol. Commun.2018614310.1186/s40478‑018‑0543‑z 29298724
     [Google Scholar]
  62. LaryeaE.T. Phosphorylation Patterns, Aggregation Propensities, and Morphological Studies of the Various Tau Protein Isoforms.Doctoral dissertation, Oakland University
     [Google Scholar]
  63. BoyarkoB. HookV. Human tau isoforms and proteolysis for production of toxic tau fragments in neurodegeneration.Front. Neurosci.20211570278810.3389/fnins.2021.702788 34744602
     [Google Scholar]
  64. BaoC. BajramiB. MarcotteD.J. Mechanisms of regulation and diverse activities of tau-tubulin kinase (TTBK) isoforms.Cell. Mol. Neurobiol.202141466968510.1007/s10571‑020‑00875‑6 32424773
     [Google Scholar]
  65. GyparakiM.T. ArabA. SorokinaE.M. Tau forms oligomeric complexes on microtubules that are distinct from tau aggregates.Proc. Natl. Acad. Sci.202111819e202146111810.1073/pnas.2021461118 33952699
     [Google Scholar]
  66. AtokiA.V. AjaP.M. OndariE.N. ShinkafiT.S. Advances in Alzheimer’s disease therapeutics: Biochemistry, exploring bioactive compounds and novel approaches.Int. J. Food Prop.20232612091212710.1080/10942912.2023.2243050
     [Google Scholar]
  67. MadavY. WairkarS. PrabhakarB. Recent therapeutic strategies targeting beta amyloid and tauopathies in Alzheimer’s disease.Brain Res. Bull.201914617118410.1016/j.brainresbull.2019.01.004 30634016
     [Google Scholar]
  68. ZubčićK. HofP.R. ŠimićG. JembrekJ.M. The role of copper in tau-related pathology in Alzheimer’s disease.Front. Mol. Neurosci.20201357230810.3389/fnmol.2020.572308 33071757
     [Google Scholar]
  69. RollsM.M. ThyagarajanP. FengC. Microtubule dynamics in healthy and injured neurons.Dev. Neurobiol.202181332133210.1002/dneu.22746 32291942
     [Google Scholar]
  70. ArnstenA.F.T. DattaD. TrediciD.K. BraakH. Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer’s disease.Alzheimers Dement.202117111512410.1002/alz.12192 33075193
     [Google Scholar]
  71. AlonsoA.D. CohenL.S. Our tau tales from normal to pathological behavior.J. Alzheimers Dis.201864s1S507S51610.3233/JAD‑179906 29614672
     [Google Scholar]
  72. BarbierP. ZejneliO. MartinhoM. Role of tau as a microtubule-associated protein: Structural and functional aspects.Front. Aging Neurosci.20191120410.3389/fnagi.2019.00204 31447664
     [Google Scholar]
  73. GonzálezA. SinghS.K. ChurrucaM. MaccioniR.B. Alzheimer’s disease and tau self-assembly: In the search of the missing link.Int. J. Mol. Sci.2022238419210.3390/ijms23084192 35457009
     [Google Scholar]
  74. OakleyS.S. MainaM.B. MarshallK.E. Tau filament self-assembly and structure: Tau as a therapeutic target.Front. Neurol.20201159075410.3389/fneur.2020.590754 33281730
     [Google Scholar]
  75. AlonsoA.C. LiB. IqbalG.I. IqbalK. Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity.Proc. Natl. Acad. Sci.2006103238864886910.1073/pnas.0603214103 16735465
     [Google Scholar]
  76. ChouhanA.K. GuoC. HsiehY.C. Uncoupling neuronal death and dysfunction in Drosophila models of neurodegenerative disease.Acta Neuropathol. Commun.2016416210.1186/s40478‑016‑0333‑4 27338814
     [Google Scholar]
  77. SochockaM. ZwolińskaK. LeszekJ. The infectious etiology of Alzheimer’s disease.Curr. Neuropharmacol.20171579961009 28294067
     [Google Scholar]
  78. WeaverD.F. Alzheimer’s disease as an innate autoimmune disease (AD 2): A new molecular paradigm.Alzheimers Dement.20231931086109810.1002/alz.12789 36165334
     [Google Scholar]
  79. ChatanakaM.K. SohaeiD. DiamandisE.P. PrassasI. Beyond the amyloid hypothesis: How current research implicates autoimmunity in Alzheimer’s disease pathogenesis.Crit. Rev. Clin. Lab. Sci.202360639842610.1080/10408363.2023.2187342 36941789
     [Google Scholar]
  80. LiJ. WangL. ZengQ. MKP 1 regulates the inflammatory activation of microglia against Alzheimer’s disease.CNS Neurosci. Ther.2023302e14409 37602891
     [Google Scholar]
  81. StephensonM.F.S. StephensonM.V.C. CarterM.D. Alzheimer’s disease as an autoimmune disorder of innate immunity endogenously modulated by tryptophan metabolites.Alzheimers Dement.202281e1228310.1002/trc2.12283 35415204
     [Google Scholar]
  82. GovindpaniK. McNamaraL.G. SmithN.R. Vascular dysfunction in Alzheimer’s disease: A prelude to the pathological process or a consequence of it?J. Clin. Med.20198565110.3390/jcm8050651 31083442
     [Google Scholar]
  83. HaysC.C. ZlatarZ.Z. WierengaC.E. The utility of cerebral blood flow as a biomarker of preclinical Alzheimer’s disease.Cell. Mol. Neurobiol.201636216717910.1007/s10571‑015‑0261‑z 26898552
     [Google Scholar]
  84. MehtaR.I. MehtaR.I. The Vascular-Immune Hypothesis of Alzheimer’s Disease.Biomedicines202311240810.3390/biomedicines11020408 36830944
     [Google Scholar]
  85. CustodiaA. OuroA. SanjurjoR.D. Endothelial progenitor cells and vascular alterations in Alzheimer’s disease.Front. Aging Neurosci.20221381121010.3389/fnagi.2021.811210 35153724
     [Google Scholar]
  86. InoueY. ShueF. BuG. KanekiyoT. Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease.Mol. Neurodegener.20231814610.1186/s13024‑023‑00640‑5 37434208
     [Google Scholar]
  87. ThakurS. DhapolaR. SarmaP. MedhiB. ReddyD.H. Neuroinflammation in Alzheimer’s disease: Current progress in molecular signaling and therapeutics.Inflammation202346111710.1007/s10753‑022‑01721‑1 35986874
     [Google Scholar]
  88. EisenmengerL.B. PeretA. FamakinB.M. Vascular contributions to Alzheimer’s disease.Transl. Res.20232544153 36529160
     [Google Scholar]
  89. RazaniE. SigaroodiP.A. AzarS.A. ZoghiA. BavarsadS.M. BashashD. The PI3K/Akt signaling axis in Alzheimer’s disease: A valuable target to stimulate or suppress?Cell Stress Chaperones202126687188710.1007/s12192‑021‑01231‑3 34386944
     [Google Scholar]
  90. MahboobifardF. PourgholamiM.H. JorjaniM. Estrogen as a key regulator of energy homeostasis and metabolic health.Biomed. Pharmacother.202215611380810.1016/j.biopha.2022.113808 36252357
     [Google Scholar]
  91. YinF. YaoJ. SanchetiH. The perimenopausal aging transition in the female rat brain: Decline in bioenergetic systems and synaptic plasticity.Neurobiol. Aging20153672282229510.1016/j.neurobiolaging.2015.03.013 25921624
     [Google Scholar]
  92. DingF. YaoJ. RettbergJ.R. ChenS. BrintonR.D. Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer’s mouse brain: Implication for bioenergetic intervention.PLoS One2013811e7997710.1371/journal.pone.0079977 24244584
     [Google Scholar]
  93. RettbergJ.R. DangH. HodisH.N. Identifying postmenopausal women at risk for cognitive decline within a healthy cohort using a panel of clinical metabolic indicators: Potential for detecting an at-Alzheimer’s risk metabolic phenotype.Neurobiol. Aging20164015516310.1016/j.neurobiolaging.2016.01.011 26973115
     [Google Scholar]
  94. BhatiaS. RawalR. SharmaP. SinghT. SinghM. SinghV. Mitochondrial dysfunction in Alzheimer’s disease: Opportunities for drug development.Curr. Neuropharmacol.202220467569210.2174/1570159X19666210517114016 33998995
     [Google Scholar]
  95. ZhangS. ZhangY. WenZ. Cognitive dysfunction in diabetes: Abnormal glucose metabolic regulation in the brain.Front. Endocrinol.202314119260210.3389/fendo.2023.1192602 37396164
     [Google Scholar]
  96. DanielJ.M. LindseyS.H. MostanyR. SchraderL.A. ZsombokA. Cardiometabolic health, menopausal estrogen therapy and the brain: How effects of estrogens diverge in healthy and unhealthy preclinical models of aging.Front. Neuroendocrinol.20237010106810.1016/j.yfrne.2023.101068 37061205
     [Google Scholar]
  97. IllianoP. BrambillaR. ParoliniC. The mutual interplay of gut microbiota, diet and human disease.FEBS J.2020287583385510.1111/febs.15217 31955527
     [Google Scholar]
  98. De la FuenteM. The role of the microbiota-gut-brain axis in the health and illness condition: A focus on Alzheimer’s disease.J. Alzheimers Dis.20218141345136010.3233/JAD‑201587 33935086
     [Google Scholar]
  99. FungT.C. The microbiota-immune axis as a central mediator of gut-brain communication.Neurobiol. Dis.202013610471410.1016/j.nbd.2019.104714 31846737
     [Google Scholar]
  100. MartinC.R. OsadchiyV. KalaniA. MayerE.A. The brain-gut-microbiome axis.Cell. Mol. Gastroenterol. Hepatol.20186213314810.1016/j.jcmgh.2018.04.003 30023410
     [Google Scholar]
  101. CussottoS. SandhuK.V. DinanT.G. CryanJ.F. The neuroendocrinology of the microbiota-gut-brain axis: A behavioural perspective.Front. Neuroendocrinol.2018518010110.1016/j.yfrne.2018.04.002 29753796
     [Google Scholar]
  102. YoshikawaS. TaniguchiK. SawamuraH. IkedaY. TsujiA. MatsudaS. A New Concept of Associations between Gut Microbiota, Immunity and Central Nervous System for the Innovative Treatment of Neurodegenerative Disorders.Metabolites20221211105210.3390/metabo12111052 36355135
     [Google Scholar]
  103. VaresiA. PierellaE. RomeoM. The potential role of gut microbiota in Alzheimer’s disease: From diagnosis to treatment.Nutrients202214366810.3390/nu14030668 35277027
     [Google Scholar]
  104. ZerdanB.M. HebboE. HijaziA. The gut microbiome and Alzheimer’s disease: A growing relationship.Curr. Alzheimer Res.2022191280881810.2174/1567205020666221227090125 36578263
     [Google Scholar]
  105. FishP.V. SteadmanD. BayleE.D. WhitingP. New approaches for the treatment of Alzheimer’s disease.Bioorg. Med. Chem. Lett.201929212513310.1016/j.bmcl.2018.11.034 30501965
     [Google Scholar]
  106. PangalosM.N. SchechterL.E. HurkoO. Drug development for CNS disorders: Strategies for balancing risk and reducing attrition.Nat. Rev. Drug Discov.20076752153210.1038/nrd2094 17599084
     [Google Scholar]
  107. AnsariA.J. MonawwarM. FatimaN. The Pathophysiology, Diagnosis and Some Management Approaches of Alzheimer’s Disease: An Overview.Drug Design Dis.202182117
     [Google Scholar]
  108. SperlingR. HenleyD. AisenP.S. Findings of efficacy, safety, and biomarker outcomes of atabecestat in preclinical Alzheimer disease: A truncated randomized phase 2b/3 clinical trial.JAMA Neurol.202178329330110.1001/jamaneurol.2020.4857 33464300
     [Google Scholar]
  109. DunnB. SteinP. CavazzoniP. Approval of aducanumab for Alzheimer disease—the FDA’s perspective.JAMA Intern. Med.2021181101276127810.1001/jamainternmed.2021.4607 34254984
     [Google Scholar]
  110. FerreroJ. WilliamsL. StellaH. First‐in‐human, double‐blind, placebo‐controlled, single‐dose escalation study of aducanumab (BIIB037) in mild‐to‐moderate Alzheimer’s disease.Alzheimers Dement.20162316917610.1016/j.trci.2016.06.002 29067304
     [Google Scholar]
  111. HaoY. DongM. SunY. DuanX. NiuW. Effectiveness and safety of monoclonal antibodies against amyloid-beta vis-à-vis placebo in mild or moderate Alzheimer’s disease.Front. Neurol.202314114775710.3389/fneur.2023.1147757 37006475
     [Google Scholar]
  112. AbushoukA.I. ElmaraezyA. AglanA. Bapineuzumab for mild to moderate Alzheimer’s disease: A meta-analysis of randomized controlled trials.BMC Neurol.20171716610.1186/s12883‑017‑0850‑1 28376794
     [Google Scholar]
  113. SperlingR.A. DonohueM.C. RamanR. Trial of solanezumab in preclinical Alzheimer’s disease.N. Engl. J. Med.2023389121096110710.1056/NEJMoa2305032 37458272
     [Google Scholar]
  114. GandyS. SanoM. Solanezumab—prospects for meaningful interventions in AD?Nat. Rev. Neurol.2015111266967010.1038/nrneurol.2015.218 26526537
     [Google Scholar]
  115. van DyckC.H. SwansonC.J. AisenP. Lecanemab in early Alzheimer’s disease.N. Engl. J. Med.2023388192110.1056/NEJMoa2212948 36449413
     [Google Scholar]
  116. FDA News ReleaseFDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval.2023Available from: https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval#:~:text=Action%20Follows%20Confirmatory%20Trial%20to%20Verify%20Clinical%20Benefit&text=Today%2C%20the%20U.S.%20Food%20and,confirmatory%20trial%20verified%20clinical%20benefit
    [Google Scholar]
  117. KumarD. AshrafM.G. BilgramiA.L. HassanI.M. Emerging therapeutic developments in neurodegenerative diseases: A clinical investigation.Drug Discov. Today2022271010330510.1016/j.drudis.2022.06.005 35728774
     [Google Scholar]
  118. BohrmannB. BaumannK. BenzJ. Gantenerumab: A novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β.J. Alzheimers Dis.2012281496910.3233/JAD‑2011‑110977 21955818
     [Google Scholar]
  119. BatemanR.J. CummingsJ. SchobelS. Gantenerumab: An anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimer’s disease.Alzheimers Res. Ther.202214117810.1186/s13195‑022‑01110‑8 36447240
     [Google Scholar]
  120. RashadA. RasoolA. ShaheryarM. Donanemab for Alzheimer’s disease: A systematic review of clinical trials.InHealthcare20221113210.3390/healthcare11010032
     [Google Scholar]
  121. NicollJ.A.R. BucklandG.R. HarrisonC.H. Persistent neuropathological effects 14 years following amyloid-β immunization in Alzheimer’s disease.Brain201914272113212610.1093/brain/awz142 31157360
     [Google Scholar]
  122. MorenoP.T. AcedoG.A. DomínguezR.A. Therapeutic approach to Alzheimer’s disease: Current treatments and new perspectives.Pharmaceutics2022146111710.3390/pharmaceutics14061117 35745693
     [Google Scholar]
  123. KhanS. BarveK.H. KumarM.S. Recent advancements in pathogenesis, diagnostics and treatment of Alzheimer’s disease.Curr. Neuropharmacol.202018111106112510.2174/1570159X18666200528142429 32484110
     [Google Scholar]
  124. WilliamsC. KindermansM. ParmentierF. Study of the mechanism of action of Blarcamesine (ANAVEX®2‐73): Whole blood transcriptomics analysis identifies treatment impact on compensatory pathways by restoring key neurodegenerative pathways functionality, including Alzheimer’s disease pathway.Alzheimers Dement.202319S7e05902410.1002/alz.059024
     [Google Scholar]
  125. PinhoT.S. CorreiaS.C. PerryG. AmbrósioA.F. MoreiraP.I. Diminished O-GlcNAcylation in Alzheimer’s disease is strongly correlated with mitochondrial anomalies.Biochim. Biophys. Acta Mol. Basis Dis.2019186582048205910.1016/j.bbadis.2018.10.037 30412792
     [Google Scholar]
  126. BartholdD. JoyceG. WhartonW. KehoeP. ZissimopoulosJ. The association of multiple anti-hypertensive medication classes with Alzheimer’s disease incidence across sex, race, and ethnicity.PLoS One20181311e020670510.1371/journal.pone.0206705 30383807
     [Google Scholar]
  127. KhalifaM. SafarM.M. AbdelsalamR.M. ZakiH.F. Telmisartan protects against aluminum-induced Alzheimer-like pathological changes in rats.Neurotox. Res.202037227528510.1007/s12640‑019‑00085‑z 31332715
     [Google Scholar]
  128. NovakP. ZilkaN. ZilkovaM. AADvac1, an active immunotherapy for Alzheimer’s disease and non Alzheimer tauopathies: An overview of preclinical and clinical development.JPAD-J PREV ALZHEIM2019616369 30569088
     [Google Scholar]
  129. PanzaF. SolfrizziV. SeripaD. Tau-based therapeutics for Alzheimer’s disease: Active and passive immunotherapy.Immunotherapy2016891119113410.2217/imt‑2016‑0019 27485083
     [Google Scholar]
  130. TengE. ManserP.T. PickthornK. Safety and efficacy of semorinemab in individuals with prodromal to mild Alzheimer disease: A randomized clinical trial.JAMA Neurol.202279875876710.1001/jamaneurol.2022.1375 35696185
     [Google Scholar]
  131. PengY. JinH. XueY. Current and future therapeutic strategies for Alzheimer’s disease: An overview of drug development bottlenecks.Front. Aging Neurosci.202315120657210.3389/fnagi.2023.1206572 37600514
     [Google Scholar]
  132. (a AbyadehM. GuptaV. GuptaV. Comparative analysis of aducanumab, zagotenemab and pioglitazone as targeted treatment strategies for Alzheimer’s disease.Aging Dis.20211281964197610.14336/AD.2021.0719 34881080
     [Google Scholar]
  133. (b ChaiX. WuS. MurrayT.K. KinleyR. CellaC.V. SimsH. BucknerN. HanmerJ. DaviesP. O’NeillM.J. HuttonM.L. Passive immunization with anti-Tau antibodies in two transgenic models: reduction of Tau pathology and delay of disease progression.J. Biol. Chem.2011286393445734467
     [Google Scholar]
  134. DuH. MengX. YaoY. XuJ. The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer’s disease.Front. Endocrinol.202213103347910.3389/fendo.2022.1033479 36465634
     [Google Scholar]
  135. PengX. ShiX. HuangJ. Exendin-4 Improves Cognitive Function of Diabetic Mice via Increasing Brain Insulin Synthesis.Curr. Alzheimer Res.202118754655710.2174/1567205018666210929150004 34587885
     [Google Scholar]
  136. GadS.N. NofalS. RaafatE.M. AhmedA.A.E. Lixisenatide reduced damage in hippocampus CA1 neurons in a rat model of cerebral ischemia-reperfusion possibly via the ERK/P38 signaling pathway.J. Mol. Neurosci.20207071026103710.1007/s12031‑020‑01497‑9 32040827
     [Google Scholar]
  137. ZhouM. ChenS. PengP. Dulaglutide ameliorates STZ induced AD-like impairment of learning and memory ability by modulating hyperphosphorylation of tau and NFs through GSK3β.Biochem. Biophys. Res. Commun.2019511115416010.1016/j.bbrc.2019.01.103 30773255
     [Google Scholar]
  138. ChangY. ZhangD. HuW. LiuD. LiL. Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis.J. Clin. Neurosci.20208123423910.1016/j.jocn.2020.09.054 33222922
     [Google Scholar]
  139. DuarteA.I. CandeiasE. AlvesI.N. Liraglutide protects against brain amyloid-β1–42 accumulation in female mice with early Alzheimer’s disease-like pathology by partially rescuing oxidative/nitrosative stress and inflammation.Int. J. Mol. Sci.2020215174610.3390/ijms21051746 32143329
     [Google Scholar]
  140. JantrapiromS. NimlamoolW. ChattipakornN. Liraglutide suppresses tau hyperphosphorylation, amyloid beta accumulation through regulating neuronal insulin signaling and BACE-1 activity.Int. J. Mol. Sci.2020215172510.3390/ijms21051725 32138327
     [Google Scholar]
  141. FemminellaGD FrangouE LoveSB Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer’s disease: Study protocol for a randomised controlled trial (ELAD study).Trials2019201-0.118
     [Google Scholar]
  142. KarkhahA. SaadiM. PourabdolhosseinF. SalekiK. NouriH.R. Indomethacin attenuates neuroinflammation and memory impairment in an STZ-induced model of Alzheimer’s like disease.Immunopharmacol. Immunotoxicol.202143675876610.1080/08923973.2021.1981374 34585992
     [Google Scholar]
  143. A Randomized Open-Label, Multiple Dose Clinical Pharmacology Study of Two Doses of a Selective p38 MAP Kinase Inhibitor, VX-745 in Patients With Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease (AD) or With Mild AD.2019Available from: https://adisinsight.springer.com/trials/700256232
  144. KesikaP. SuganthyN. SivamaruthiB.S. ChaiyasutC. Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer’s disease.Life Sci.202126411862710.1016/j.lfs.2020.118627 33169684
     [Google Scholar]
  145. AslR.Z. SepehriG. SalamiM. Probiotic treatment improves the impaired spatial cognitive performance and restores synaptic plasticity in an animal model of Alzheimer’s disease.Behav. Brain Res.201937611218310.1016/j.bbr.2019.112183 31472194
     [Google Scholar]
  146. JeongJ.J. WooJ.Y. KimK.A. HanM.J. KimD.H. Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent memory impairment in Fischer 344 rats.Lett. Appl. Microbiol.201560430731410.1111/lam.12393 25598393
     [Google Scholar]
  147. NimgampalleM. KunaY. Anti-Alzheimer properties of probiotic, Lactobacillus plantarum MTCC 1325 in Alzheimer’s disease induced albino rats.J. Clin. Diagn. Res.2017118KC01KC0510.7860/JCDR/2017/26106.10428 28969160
     [Google Scholar]
  148. KobayashiY. SugaharaH. ShimadaK. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer’s disease.Sci. Rep.2017711351010.1038/s41598‑017‑13368‑2 29044140
     [Google Scholar]
  149. MafteiN.M. Probiotic, prebiotic and synbiotic products in human health.Front New Trends Sci Fermented Food Beverag.IntechOpen201911910.5772/intechopen.81553
     [Google Scholar]
  150. BonfiliL. CecariniV. CuccioloniM. SLAB51 probiotic formulation activates SIRT1 pathway promoting antioxidant and neuroprotective effects in an AD mouse model.Mol. Neurobiol.201855107987800010.1007/s12035‑018‑0973‑4 29492848
     [Google Scholar]
  151. WestfallS. LomisN. PrakashS. A novel synbiotic delays Alzheimer’s disease onset via combinatorial gut-brain-axis signaling in Drosophila melanogaster.PLoS One2019144e021498510.1371/journal.pone.0214985 31009489
     [Google Scholar]
  152. SuganyaK. KooB.S. Gut–brain axis: Role of gut microbiota on neurological disorders and how probiotics/prebiotics beneficially modulate microbial and immune pathways to improve brain functions.Int. J. Mol. Sci.20202120755110.3390/ijms21207551 33066156
     [Google Scholar]
  153. MoriiK.F. FriedlandR.P. YoshidaH. MizunoT. Drosophila as a model for microbiota studies of neurodegeneration.J. Alzheimers Dis.202184247949010.3233/JAD‑215031 34569965
     [Google Scholar]
  154. EbrahimiV. TarhrizV. TalebiM. A new insight on feasibility of pre-, pro-, and synbiotics-based therapies in Alzheimer’s disease.J Reports in Pharm Sci202211214115510.4103/jrptps.JRPTPS_170_21
     [Google Scholar]
/content/journals/cdth/10.2174/0115748855307998240529063710
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Current Treatment Approaches for Alzheimer’s Disease and Possible Drug Targets
Curr Drug Ther 20, 674 (2025); https://doi.org/10.2174/0115748855307998240529063710
/content/journals/cdth/10.2174/0115748855307998240529063710
/content/journals/cdth/10.2174/0115748855307998240529063710
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  • Article Type:     Review Article
Keyword(s): Alzheimer’s disease; anti-amyloid therapy; antibody therapy; autoimmunity; dementia; gut microbiota

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