Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Alzheimer Research
  4. Fast Track Articles
  5. Fast Track Article
image of Recent Updates on Alzheimer’s Disease: Pathogenesis, Pathophysiology, Molecular Approaches and Natural Bioactive Compounds Used in Contemporary Time to Alleviate Disease

Abstract

Alzheimer's disease (AD), characterised by gradual memory loss and neurodegeneration, is an important risk to global health. Despite the recent advances in the field of neuroscience, the complex biological mechanisms underlying the aetiology and pathology of AD have not been elucidated yet. The development of amyloid-beta plaques, hyperphosphorylation of tau protein, oxidative stress, and neuroinflammation have been identified as important components. The genesis of AD has been illuminated by advances in molecular techniques, which have shown the contributions of environmental, genetic, and epigenetic variables.

Ongoing research is focused on the potential of bioactive compounds as therapeutic agents. Quercetin, epigallocatechin gallate, huperzine A, ginsenosides, omega-3 fatty acids, vitamin E, zinc, bacosides from brahmi, and withanolide A from ashwagandha are among the compounds that have demonstrated encouraging effects in modifying disease pathways. These bioactive substances demonstrate their potential for symptomatic relief by providing neuroprotective, antioxidant, anti-inflammatory, and cognitive-enhancing properties. The present review presents the recent findings on AD pathogenesis, molecular mechanisms, and the impact of natural compounds, offering a comprehensive perspective on current and emerging strategies for managing this debilitating condition.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/car/10.2174/0115672050361294241211071813
2024-12-23
2025-01-18

  • From This Site

    /content/journals/car/10.2174/0115672050361294241211071813
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Wilson R.S. Segawa E. Boyle P.A. Anagnos S.E. Hizel L.P. Bennett D.A. The natural history of cognitive decline in Alzheimer’s disease. Psychol. Aging 2012 27 4 1008 1017 10.1037/a0029857 22946521
    [Google Scholar]
  2. Musiek E.S. Holtzman D.M. Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science 2016 354 6315 1004 1008 10.1126/science.aah4968 27885006
    [Google Scholar]
  3. Yiannopoulou K.G. Papageorgiou S.G. Current and future treatments in alzheimer disease: An update. J. Cent. Nerv. Syst. Dis. 2020 12 10.1177/1179573520907397 32165850
    [Google Scholar]
  4. Long J.M. Holtzman D.M. Alzheimer disease: An update on pathobiology and treatment strategies. Cell 2019 179 2 312 339 10.1016/j.cell.2019.09.001 31564456
    [Google Scholar]
  5. Li X.L. Hu N. Tan M.S. Yu J.T. Tan L. Behavioral and psychological symptoms in Alzheimer’s disease. BioMed Res. Int. 2014 2014 1 9 10.1155/2014/927804 25133184
    [Google Scholar]
  6. Selkoe D.J. Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol. Med. 2016 8 6 595 608 10.15252/emmm.201606210 27025652
    [Google Scholar]
  7. Heneka M.T. Golenbock D.T. Latz E. Innate immunity in Alzheimer’s disease. Nat. Immunol. 2015 16 3 229 236 10.1038/ni.3102 25689443
    [Google Scholar]
  8. Hsu J.W. Willis R.J. Dementia risk and financial decision making by older households: The impact of information. SSRN 2013 2013 45 56 10.2139/ssrn.2339225 25525476
    [Google Scholar]
  9. Karch C.M. Goate A.M. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol. Psychiatry 2015 77 1 43 51 10.1016/j.biopsych.2014.05.006 24951455
    [Google Scholar]
  10. Lane C.A. Hardy J. Schott J.M. Alzheimer’s disease. Eur. J. Neurol. 2018 25 1 59 70 10.1111/ene.13439 28872215
    [Google Scholar]
  11. Rajmohan R. Reddy P.H. Amyloid-beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer’s disease neurons. J. Alzheimers Dis. 2017 57 4 975 999 10.3233/JAD‑160612 27567878
    [Google Scholar]
  12. Anoop A. Singh P.K. Jacob R.S. Maji S.K. CSF biomarkers for alzheimer’s disease diagnosis. Int. J. Alzheimers Dis. 2010 2010 1 12 10.4061/2010/606802 20721349
    [Google Scholar]
  13. Bales K.R. Dodart J.C. DeMattos R.B. Holtzman D.M. Paul S.M. Apolipoprotein E, amyloid, and Alzheimer disease. Mol. Interv. 2002 2 6 363 375, 339 10.1124/mi.2.6.363 14993413
    [Google Scholar]
  14. Bassett C.N. Montine T.J. Lipoproteins and lipid peroxidation in Alzheimer’s disease. J. Nutr. Health Aging 2003 7 1 24 29 12679837
    [Google Scholar]
  15. Villemagne V.L. Burnham S. Bourgeat P. Brown B. Ellis K.A. Salvado O. Szoeke C. Macaulay S.L. Martins R. Maruff P. Ames D. Rowe C.C. Masters C.L. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: A prospective cohort study. Lancet Neurol. 2013 12 4 357 367 10.1016/S1474‑4422(13)70044‑9 23477989
    [Google Scholar]
  16. Masters C.L. Bateman R. Blennow K. Rowe C.C. Sperling R.A. Cummings J.L. Alzheimer’s disease. Nat. Rev. Dis. Primers 2015 1 1 15056 10.1038/nrdp.2015.56 27188934
    [Google Scholar]
  17. Small S.A. Duff K. Linking Abeta and tau in late-onset Alzheimer’s disease: A dual pathway hypothesis. Neuron 2008 60 4 534 542 10.1016/j.neuron.2008.11.007 19038212
    [Google Scholar]
  18. Mattson M.P. Pathways towards and away from Alzheimer’s disease. Nature 2004 430 7000 631 639 10.1038/nature02621 15295589
    [Google Scholar]
  19. Hampel H. Hardy J. Blennow K. Chen C. Perry G. Kim S.H. Villemagne V.L. Aisen P. Vendruscolo M. Iwatsubo T. Masters C.L. Cho M. Lannfelt L. Cummings J.L. Vergallo A. The amyloid-β pathway in Alzheimer’s disease. Mol. Psychiatry 2021 26 10 5481 5503 10.1038/s41380‑021‑01249‑0 34456336
    [Google Scholar]
  20. Castellani R.J. Perry G. Smith M.A. The role of novel therapeutics in the treatment of Alzheimer’s disease. Expert Opin. Investig. Drugs 2007 16 6 753 766
    [Google Scholar]
  21. Mucke L. Selkoe D.J. Neurotoxicity of amyloid β-protein: Synaptic and network dysfunction. Cold Spring Harb. Perspect. Med. 2012 2 7 a006338 10.1101/cshperspect.a006338 22762015
    [Google Scholar]
  22. Hugo J. Ganguli M. Dementia and cognitive impairment: Epidemiology, diagnosis, and treatment. Clin. Geriatr. Med. 2014 30 3 421 442 10.1016/j.cger.2014.04.001 25037289
    [Google Scholar]
  23. Glenner G.G. Wong C.W. Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 1984 120 3 885 890 10.1016/S0006‑291X(84)80190‑4 6375662
    [Google Scholar]
  24. Greenberg S.M. Bacskai B.J. Hernandez-Guillamon M. Pruzin J. Sperling R. van Veluw S.J. Cerebral amyloid angiopathy and Alzheimer disease — One peptide, two pathways. Nat. Rev. Neurol. 2020 16 1 30 42 10.1038/s41582‑019‑0281‑2 31827267
    [Google Scholar]
  25. Kunkle B.W. Grenier-Boley B. Sims R. Bis J.C. Damotte V. Naj A.C. Boland A. Vronskaya M. van der Lee S.J. Amlie-Wolf A. Bellenguez C. Frizatti A. Chouraki V. Martin E.R. Sleegers K. Badarinarayan N. Jakobsdottir J. Hamilton-Nelson K.L. Moreno-Grau S. Olaso R. Raybould R. Chen Y. Kuzma A.B. Hiltunen M. Morgan T. Ahmad S. Vardarajan B.N. Epelbaum J. Hoffmann P. Boada M. Beecham G.W. Garnier J.G. Harold D. Fitzpatrick A.L. Valladares O. Moutet M.L. Gerrish A. Smith A.V. Qu L. Bacq D. Denning N. Jian X. Zhao Y. Del Zompo M. Fox N.C. Choi S.H. Mateo I. Hughes J.T. Adams H.H. Malamon J. Sanchez-Garcia F. Patel Y. Brody J.A. Dombroski B.A. Naranjo M.C.D. Daniilidou M. Eiriksdottir G. Mukherjee S. Wallon D. Uphill J. Aspelund T. Cantwell L.B. Garzia F. Galimberti D. Hofer E. Butkiewicz M. Fin B. Scarpini E. Sarnowski C. Bush W.S. Meslage S. Kornhuber J. White C.C. Song Y. Barber R.C. Engelborghs S. Sordon S. Voijnovic D. Adams P.M. Vandenberghe R. Mayhaus M. Cupples L.A. Albert M.S. De Deyn P.P. Gu W. Himali J.J. Beekly D. Squassina A. Hartmann A.M. Orellana A. Blacker D. Rodriguez-Rodriguez E. Lovestone S. Garcia M.E. Doody R.S. Munoz-Fernadez C. Sussams R. Lin H. Fairchild T.J. Benito Y.A. Holmes C. Karamujić-Čomić H. Frosch M.P. Thonberg H. Maier W. Roshchupkin G. Ghetti B. Giedraitis V. Kawalia A. Li S. Huebinger R.M. Kilander L. Moebus S. Hernández I. Kamboh M.I. Brundin R. Turton J. Yang Q. Katz M.J. Concari L. Lord J. Beiser A.S. Keene C.D. Helisalmi S. Kloszewska I. Kukull W.A. Koivisto A.M. Lynch A. Tarraga L. Larson E.B. Haapasalo A. Lawlor B. Mosley T.H. Lipton R.B. Solfrizzi V. Gill M. Longstreth W.T. Jr Montine T.J. Frisardi V. Diez-Fairen M. Rivadeneira F. Petersen R.C. Deramecourt V. Alvarez I. Salani F. Ciaramella A. Boerwinkle E. Reiman E.M. Fievet N. Rotter J.I. Reisch J.S. Hanon O. Cupidi C. Andre Uitterlinden A.G. Royall D.R. Dufouil C. Maletta R.G. de Rojas I. Sano M. Brice A. Cecchetti R. George-Hyslop P.S. Ritchie K. Tsolaki M. Tsuang D.W. Dubois B. Craig D. Wu C.K. Soininen H. Avramidou D. Albin R.L. Fratiglioni L. Germanou A. Apostolova L.G. Keller L. Koutroumani M. Arnold S.E. Panza F. Gkatzima O. Asthana S. Hannequin D. Whitehead P. Atwood C.S. Caffarra P. Hampel H. Quintela I. Carracedo Á. Lannfelt L. Rubinsztein D.C. Barnes L.L. Pasquier F. Frölich L. Barral S. McGuinness B. Beach T.G. Johnston J.A. Becker J.T. Passmore P. Bigio E.H. Schott J.M. Bird T.D. Warren J.D. Boeve B.F. Lupton M.K. Bowen J.D. Proitsi P. Boxer A. Powell J.F. Burke J.R. Kauwe J.S.K. Burns J.M. Mancuso M. Buxbaum J.D. Bonuccelli U. Cairns N.J. McQuillin A. Cao C. Livingston G. Carlson C.S. Bass N.J. Carlsson C.M. Hardy J. Carney R.M. Bras J. Carrasquillo M.M. Guerreiro R. Allen M. Chui H.C. Fisher E. Masullo C. Crocco E.A. DeCarli C. Bisceglio G. Dick M. Ma L. Duara R. Graff-Radford N.R. Evans D.A. Hodges A. Faber K.M. Scherer M. Fallon K.B. Riemenschneider M. Fardo D.W. Heun R. Farlow M.R. Kölsch H. Ferris S. Leber M. Foroud T.M. Heuser I. Galasko D.R. Giegling I. Gearing M. Hüll M. Geschwind D.H. Gilbert J.R. Morris J. Green R.C. Mayo K. Growdon J.H. Feulner T. Hamilton R.L. Harrell L.E. Drichel D. Honig L.S. Cushion T.D. Huentelman M.J. Hollingworth P. Hulette C.M. Hyman B.T. Marshall R. Jarvik G.P. Meggy A. Abner E. Menzies G.E. Jin L.W. Leonenko G. Real L.M. Jun G.R. Baldwin C.T. Grozeva D. Karydas A. Russo G. Kaye J.A. Kim R. Jessen F. Kowall N.W. Vellas B. Kramer J.H. Vardy E. LaFerla F.M. Jöckel K.H. Lah J.J. Dichgans M. Leverenz J.B. Mann D. Levey A.I. Pickering-Brown S. Lieberman A.P. Klopp N. Lunetta K.L. Wichmann H.E. Lyketsos C.G. Morgan K. Marson D.C. Brown K. Martiniuk F. Medway C. Mash D.C. Nöthen M.M. Masliah E. Hooper N.M. McCormick W.C. Daniele A. McCurry S.M. Bayer A. McDavid A.N. Gallacher J. McKee A.C. van den Bussche H. Mesulam M. Brayne C. Miller B.L. Riedel-Heller S. Miller C.A. Miller J.W. Al-Chalabi A. Morris J.C. Shaw C.E. Myers A.J. Wiltfang J. O’Bryant S. Olichney J.M. Alvarez V. Parisi J.E. Singleton A.B. Paulson H.L. Collinge J. Perry W.R. Mead S. Peskind E. Cribbs D.H. Rossor M. Pierce A. Ryan N.S. Poon W.W. Nacmias B. Potter H. Sorbi S. Quinn J.F. Sacchinelli E. Raj A. Spalletta G. Raskind M. Caltagirone C. Bossù P. Orfei M.D. Reisberg B. Clarke R. Reitz C. Smith A.D. Ringman J.M. Warden D. Roberson E.D. Wilcock G. Rogaeva E. Bruni A.C. Rosen H.J. Gallo M. Rosenberg R.N. Ben-Shlomo Y. Sager M.A. Mecocci P. Saykin A.J. Pastor P. Cuccaro M.L. Vance J.M. Schneider J.A. Schneider L.S. Slifer S. Seeley W.W. Smith A.G. Sonnen J.A. Spina S. Stern R.A. Swerdlow R.H. Tang M. Tanzi R.E. Trojanowski J.Q. Troncoso J.C. Van Deerlin V.M. Van Eldik L.J. Vinters H.V. Vonsattel J.P. Weintraub S. Welsh-Bohmer K.A. Wilhelmsen K.C. Williamson J. Wingo T.S. Woltjer R.L. Wright C.B. Yu C.E. Yu L. Saba Y. Pilotto A. Bullido M.J. Peters O. Crane P.K. Bennett D. Bosco P. Coto E. Boccardi V. De Jager P.L. Lleo A. Warner N. Lopez O.L. Ingelsson M. Deloukas P. Cruchaga C. Graff C. Gwilliam R. Fornage M. Goate A.M. Sanchez-Juan P. Kehoe P.G. Amin N. Ertekin-Taner N. Berr C. Debette S. Love S. Launer L.J. Younkin S.G. Dartigues J.F. Corcoran C. Ikram M.A. Dickson D.W. Nicolas G. Campion D. Tschanz J. Schmidt H. Hakonarson H. Clarimon J. Munger R. Schmidt R. Farrer L.A. Van Broeckhoven C. C O’Donovan M. DeStefano A.L. Jones L. Haines J.L. Deleuze J.F. Owen M.J. Gudnason V. Mayeux R. Escott-Price V. Psaty B.M. Ramirez A. Wang L.S. Ruiz A. van Duijn C.M. Holmans P.A. Seshadri S. Williams J. Amouyel P. Schellenberg G.D. Lambert J.C. Pericak-Vance M.A. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat. Genet. 2019 51 3 414 430 10.1038/s41588‑019‑0358‑2 30820047
    [Google Scholar]
  26. Bateman R.J. Xiong C. Benzinger T.L.S. Fagan A.M. Goate A. Fox N.C. Marcus D.S. Cairns N.J. Xie X. Blazey T.M. Holtzman D.M. Santacruz A. Buckles V. Oliver A. Moulder K. Aisen P.S. Ghetti B. Klunk W.E. McDade E. Martins R.N. Masters C.L. Mayeux R. Ringman J.M. Rossor M.N. Schofield P.R. Sperling R.A. Salloway S. Morris J.C. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N. Engl. J. Med. 2012 367 9 795 804 10.1056/NEJMoa1202753 22784036
    [Google Scholar]
  27. Leung K.K. Barnes J. Ridgway G.R. Bartlett J.W. Clarkson M.J. Macdonald K. Schuff N. Fox N.C. Ourselin S. Automated cross-sectional and longitudinal hippocampal volume measurement in mild cognitive impairment and Alzheimer’s disease. Neuroimage 2010 51 4 1345 1359 10.1016/j.neuroimage.2010.03.018 20230901
    [Google Scholar]
  28. Greicius M.D. Srivastava G. Reiss A.L. Menon V. Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: Evidence from functional MRI. Proc. Natl. Acad. Sci. USA 2004 101 13 4637 4642 10.1073/pnas.0308627101 15070770
    [Google Scholar]
  29. Mielke M. Vemuri P. Rocca W. Clinical epidemiology of Alzheimer’s disease: Assessing sex and gender differences. Clin. Epidemiol. 2014 6 37 48 10.2147/CLEP.S37929 24470773
    [Google Scholar]
  30. Hampel H. Hardy J. Blennow K. Amyloid-beta and tau biomarkers in Alzheimer’s disease. Trends Pharmacol. Sci. 2010 31 8 402 410
    [Google Scholar]
  31. Cummings J. Lee G. Zhong K. Fonseca J. Taghva K. Alzheimer’s disease drug development pipeline: 2021. Alzheimers Dement. 2021 7 1 e12179 10.1002/trc2.12179 34095440
    [Google Scholar]
  32. Golde T.E. Schneider L.S. Koo E.H. Anti-aβ therapeutics in Alzheimer’s disease: The need for a paradigm shift. Neuron 2011 69 2 203 213 10.1016/j.neuron.2011.01.002 21262461
    [Google Scholar]
  33. Tzioras M. McGeachan R.I. Durrant C.S. Spires-Jones T.L. Synaptic degeneration in Alzheimer disease. Nat. Rev. Neurol. 2023 19 1 19 38 10.1038/s41582‑022‑00749‑z 36513730
    [Google Scholar]
  34. Rollo M.E. Williams R.E. Stewart L.R. Molecular imaging in Alzheimer’s disease: An update on amyloid and tau imaging. Front. Aging Neurosci. 2021 13 642819
    [Google Scholar]
  35. LaFerla F.M. Green K.N. Oddo S. Intracellular amyloid-β in Alzheimer’s disease. Nat. Rev. Neurosci. 2007 8 7 499 509 10.1038/nrn2168 17551515
    [Google Scholar]
  36. Heppner F.L. Ransohoff R.M. Becher B. Immune attack: The role of inflammation in Alzheimer disease. Nat. Rev. Neurosci. 2015 16 6 358 372 10.1038/nrn3880 25991443
    [Google Scholar]
  37. Medeiros R. Baglietto-Vargas D. LaFerla F.M. The role of tau in Alzheimer’s disease and related disorders. CNS Neurosci. Ther. 2011 17 5 514 524 10.1111/j.1755‑5949.2010.00177.x 20553310
    [Google Scholar]
  38. Shi Y. Yamada K. Liddelow S.A. Smith S.T. Zhao L. Luo W. Tsai R.M. Spina S. Grinberg L.T. Rojas J.C. Gallardo G. Wang K. Roh J. Robinson G. Finn M.B. Jiang H. Sullivan P.M. Baufeld C. Wood M.W. Sutphen C. McCue L. Xiong C. Del-Aguila J.L. Morris J.C. Cruchaga C. Fagan A.M. Miller B.L. Boxer A.L. Seeley W.W. Butovsky O. Barres B.A. Paul S.M. Holtzman D.M. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 2017 549 7673 523 527 10.1038/nature24016 28959956
    [Google Scholar]
  39. Kim S. Swaminathan S. Shen L. Risacher S.L. Nho K. Foroud T. Shaw L.M. Trojanowski J.Q. Potkin S.G. Huentelman M.J. Craig D.W. DeChairo B.M. Aisen P.S. Petersen R.C. Weiner M.W. Saykin A.J. Genome-wide association study of CSF biomarkers Aβ 1-42, t-tau, and p-tau 181p in the ADNI cohort. Neurology 2011 76 1 69 79 10.1212/WNL.0b013e318204a397 21123754
    [Google Scholar]
  40. DeTure M.A. Dickson D.W. The neuropathological diagnosis of Alzheimer’s disease. Mol. Neurodegener. 2019 14 1 32 10.1186/s13024‑019‑0333‑5 31375134
    [Google Scholar]
  41. Gong C.X. Liu F. Grundke-Iqbal I. Iqbal K. Post-translational modifications of tau protein in Alzheimer’s disease. J. Neural Transm. 2005 112 6 813 838 10.1007/s00702‑004‑0221‑0 15517432
    [Google Scholar]
  42. Veitch D.P. Weiner M.W. Aisen P.S. Beckett L.A. Cairns N.J. Green R.C. Harvey D. Jack C.R. Jr Jagust W. Morris J.C. Petersen R.C. Saykin A.J. Shaw L.M. Toga A.W. Trojanowski J.Q. Understanding disease progression and improving Alzheimer’s disease clinical trials: Recent highlights from the alzheimer’s disease neuroimaging initiative. Alzheimers Dement. 2019 15 1 106 152 10.1016/j.jalz.2018.08.005 30321505
    [Google Scholar]
  43. Ghiso J. Tomidokoro Y. Revesz T. Frangione B. Rostagno A. Cerebral amyloid angiopathy and Alzheimer’s disease. Hirosaki Igaku 2010 61 Suppl. S111 S124 21037967
    [Google Scholar]
  44. Iturria-Medina Y. Sotero R.C. Toussaint P.J. Mateos-Pérez J.M. Evans A.C. Weiner M.W. Aisen P. Petersen R. Jack C.R. Jagust W. Trojanowki J.Q. Toga A.W. Beckett L. Green R.C. Saykin A.J. Morris J. Shaw L.M. Khachaturian Z. Sorensen G. Kuller L. Raichle M. Paul S. Davies P. Fillit H. Hefti F. Holtzman D. Mesulam M.M. Potter W. Snyder P. Schwartz A. Montine T. Thomas R.G. Donohue M. Walter S. Gessert D. Sather T. Jiminez G. Harvey D. Bernstein M. Fox N. Thompson P. Schuff N. Borowski B. Gunter J. Senjem M. Vemuri P. Jones D. Kantarci K. Ward C. Koeppe R.A. Foster N. Reiman E.M. Chen K. Mathis C. Landau S. Cairns N.J. Householder E. Taylor-Reinwald L. Lee V. Korecka M. Figurski M. Crawford K. Neu S. Foroud T.M. Potkin S. Shen L. Faber K. Kim S. Nho K. Thal L. Buckholtz N. Albert M. Frank R. Hsiao J. Kaye J. Quinn J. Lind B. Carter R. Dolen S. Schneider L.S. Pawluczyk S. Beccera M. Teodoro L. Spann B.M. Brewer J. Vanderswag H. Fleisher A. Heidebrink J.L. Lord J.L. Mason S.S. Albers C.S. Knopman D. Johnson K. Doody R.S. Villanueva-Meyer J. Chowdhury M. Rountree S. Dang M. Stern Y. Honig L.S. Bell K.L. Ances B. Carroll M. Leon S. Mintun M.A. Schneider S. Oliver A. Marson D. Griffith R. Clark D. Geldmacher D. Brockington J. Roberson E. Grossman H. Mitsis E. de Toledo-Morrell L. Shah R.C. Duara R. Varon D. Greig M.T. Roberts P. Albert M. Onyike C. D’Agostino D. Kielb S. Galvin J.E. Cerbone B. Michel C.A. Rusinek H. de Leon M.J. Glodzik L. De Santi S. Doraiswamy P.M. Petrella J.R. Wong T.Z. Arnold S.E. Karlawish J.H. Wolk D. Smith C.D. Jicha G. Hardy P. Sinha P. Oates E. Conrad G. Lopez O.L. Oakley M.A. Simpson D.M. Porsteinsson A.P. Goldstein B.S. Martin K. Makino K.M. Ismail M.S. Brand C. Mulnard R.A. Thai G. Mc-Adams-Ortiz C. Womack K. Mathews D. Quiceno M. Diaz-Arrastia R. King R. Weiner M. Martin-Cook K. DeVous M. Levey A.I. Lah J.J. Cellar J.S. Burns J.M. Anderson H.S. Swerdlow R.H. Apostolova L. Tingus K. Woo E. Silverman D.H.S. Lu P.H. Bartzokis G. Graff-Radford N.R. Parfitt F. Kendall T. Johnson H. Farlow M.R. Hake A.M. Matthews B.R. Herring S. Hunt C. van Dyck C.H. Carson R.E. MacAvoy M.G. Chertkow H. Bergman H. Hosein C. Black S. Stefanovic B. Caldwell C. Hsiung G-Y.R. Feldman H. Mudge B. Assaly M. Kertesz A. Rogers J. Bernick C. Munic D. Kerwin D. Mesulam M-M. Lipowski K. Wu C-K. Johnson N. Sadowsky C. Martinez W. Villena T. Turner R.S. Johnson K. Reynolds B. Sperling R.A. Johnson K.A. Marshall G. Frey M. Lane B. Rosen A. Tinklenberg J. Sabbagh M.N. Belden C.M. Jacobson S.A. Sirrel S.A. Kowall N. Killiany R. Budson A.E. Norbash A. Johnson P.L. Allard J. Lerner A. Ogrocki P. Hudson L. Fletcher E. Carmichael O. Olichney J. DeCarli C. Kittur S. Borrie M. Lee T-Y. Bartha R. Johnson S. Asthana S. Carlsson C.M. Potkin S.G. Preda A. Nguyen D. Tariot P. Reeder S. Bates V. Capote H. Rainka M. Scharre D.W. Kataki M. Adeli A. Zimmerman E.A. Celmins D. Brown A.D. Pearlson G.D. Blank K. Anderson K. Santulli R.B. Kitzmiller T.J. Schwartz E.S. Sink K.M. Williamson J.D. Garg P. Watkins F. Ott B.R. Querfurth H. Tremont G. Salloway S. Malloy P. Correia S. Rosen H.J. Miller B.L. Mintzer J. Spicer K. Bachman D. Finger E. Pasternak S. Rachinsky I. Drost D. Pomara N. Hernando R. Sarrael A. Schultz S.K. Ponto L.L.B. Shim H. Smith K.E. Relkin N. Chaing G. Raudin L. Smith A. Fargher K. Raj B.A. Neylan T. Grafman J. Davis M. Morrison R. Hayes J. Finley S. Friedl K. Fleischman D. Arfanakis K. James O. Massoglia D. Fruehling J.J. Harding S. Peskind E.R. Petrie E.C. Li G. Yesavage J.A. Taylor J.L. Furst A.J. Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis. Nat. Commun. 2016 7 1 11934 10.1038/ncomms11934 27327500
    [Google Scholar]
  45. Selkoe D.J. Resolving controversies on the path to Alzheimer’s therapeutics. Nat. Med. 2011 17 9 1060 1065 10.1038/nm.2460 21900936
    [Google Scholar]
  46. Zhao Y. Zhao B. Oxidative stress and the pathogenesis of Alzheimer’s disease. Oxid. Med. Cell. Longev. 2013 2013 1 10 10.1155/2013/316523 23983897
    [Google Scholar]
  47. Wang JZ Xia YY Grundke-Iqbal I Iqbal K Abnormal hyperphosphorylation of tau: Sites, regulation, and molecular mechanism of neurofibrillary degeneration. J. Alzheimers Dis. 2013 33 Suppl 1
    [Google Scholar]
  48. Ferri C.P. Prince M. Brayne C. Brodaty H. Fratiglioni L. Ganguli M. Hall K. Hasegawa K. Hendrie H. Huang Y. Jorm A. Mathers C. Menezes P.R. Rimmer E. Scazufca M. Global prevalence of dementia: A Delphi consensus study. Lancet 2005 366 9503 2112 2117 10.1016/S0140‑6736(05)67889‑0 16360788
    [Google Scholar]
  49. Ballard C. Gauthier S. Corbett A. Brayne C. Aarsland D. Jones E. Alzheimer’s disease. Lancet 2011 377 9770 1019 1031 10.1016/S0140‑6736(10)61349‑9 21371747
    [Google Scholar]
  50. Pluta R. A look at the etiology of Alzheimer’s disease based on the brain ischemia model. Curr. Alzheimer Res. 2024 21 3 166 182 10.2174/0115672050320921240627050736 38963100
    [Google Scholar]
  51. Mullane K. Williams M. Alzheimer’s therapeutics: Continued clinical failures question the validity of the amyloid hypothesis—but what lies beyond? Biochem. Pharmacol. 2013 85 3 289 305 10.1016/j.bcp.2012.11.014 23178653
    [Google Scholar]
  52. Edison P. Archer H.A. Hinz R. Hammers A. Pavese N. Tai Y.F. Hotton G. Cutler D. Fox N. Kennedy A. Rossor M. Brooks D.J. Amyloid, hypometabolism, and cognition in Alzheimer disease. Neurology 2007 68 7 501 508 10.1212/01.wnl.0000244749.20056.d4 17065593
    [Google Scholar]
  53. Canter R.G. Penney J. Tsai L.H. The road to restoring neural circuits for the treatment of Alzheimer’s disease. Nature 2016 539 7628 187 196 10.1038/nature20412 27830780
    [Google Scholar]
  54. Khan S. Barve K.H. Kumar M.S. Recent advancements in pathogenesis, diagnostic and therapeutic insights of Alzheimer’s disease. Biomed. Pharmacother. 2020 128 110310
    [Google Scholar]
  55. Holtzman D.M. Morris J.C. Goate A.M. Alzheimer’s disease: The challenge of the second century. Sci. Transl. Med. 2011 3 77 77sr1 10.1126/scitranslmed.3002369 21471435
    [Google Scholar]
  56. Guerreiro R. Bras J. The age factor in Alzheimer’s disease. Genome Med. 2015 7 1 106 112 10.1186/s13073‑015‑0232‑5 26482651
    [Google Scholar]
  57. Blennow K. Zetterberg H. Biomarkers for Alzheimer’s disease: Current status and prospects for the future. J. Intern. Med. 2018 284 6 643 663 10.1111/joim.12816 30051512
    [Google Scholar]
  58. Talboom J.S. Håberg A. De Both M.D. Naymik M.A. Schrauwen I. Lewis C.R. Bertinelli S.F. Hammersland C. Fritz M.A. Myers A.J. Hay M. Barnes C.A. Glisky E. Ryan L. Huentelman M.J. Family history of Alzheimer’s disease alters cognition and is modified by medical and genetic factors. eLife 2019 8 e46179 10.7554/eLife.46179 31210642
    [Google Scholar]
  59. Tanzi R.E. The genetics of Alzheimer disease. Cold Spring Harb. Perspect. Med. 2012 2 10 a006296 10.1101/cshperspect.a006296 23028126
    [Google Scholar]
  60. Mielke M.M. Sex and gender differences in Alzheimer’s disease dementia. Psychiatr. Times 2018 35 11 14 17 30820070
    [Google Scholar]
  61. Leszek J. Mikhaylenko E.V. Belousov D.M. Koutsouraki E. Szczechowiak K. Kobusiak-Prokopowicz M. Mysiak A. Diniz B.S. Somasundaram S.G. Kirkland C.E. Aliev G. The links between cardiovascular diseases and alzheimer’s disease. Curr. Neuropharmacol. 2021 19 2 152 169 10.2174/18756190MTA4dNjE52 32727331
    [Google Scholar]
  62. Dhana K. Evans D.A. Rajan K.B. Bennett D.A. Morris M.C. Healthy lifestyle and the risk of Alzheimer dementia. Neurology 2020 95 4 e374 e383 10.1212/WNL.0000000000009816 32554763
    [Google Scholar]
  63. Mielke M.M. Ransom J.E. Mandrekar J. Turcano P. Savica R. Brown A.W. Traumatic brain injury and risk of Alzheimer’s disease and related dementias in the population. J. Alzheimers Dis. 2022 88 3 1049 1059 10.3233/JAD‑220159 35723103
    [Google Scholar]
  64. Wilson R.S. Yu L. Lamar M. Schneider J.A. Boyle P.A. Bennett D.A. Education and cognitive reserve in old age. Neurology 2019 92 10 e1041 e1050 10.1212/WNL.0000000000007036 30728309
    [Google Scholar]
  65. Passeri E. Elkhoury K. Morsink M. Broersen K. Linder M. Tamayol A. Malaplate C. Yen F.T. Arab-Tehrany E. Alzheimer’s disease: Treatment strategies and their limitations. Int. J. Mol. Sci. 2022 23 22 13954 10.3390/ijms232213954 36430432
    [Google Scholar]
  66. Shi L. Baitaluk M. Ning S. TREM2-dependent effects on Tau pathology in a mouse model of Alzheimer’s disease. Cell Rep. 2017 21 9 2585 2595 29186693
    [Google Scholar]
  67. Frost G.R. Li Y.M. The role of astrocytes in amyloid production and Alzheimer’s disease. Open Biol. 2017 7 12 170228 10.1098/rsob.170228 29237809
    [Google Scholar]
  68. Liu J. Chang L. Song Y. Li H. Wu Y. The role of NMDA receptors in Alzheimer’s disease. Front. Neurosci. 2019 13 43 10.3389/fnins.2019.00043 30800052
    [Google Scholar]
  69. Yang Y. Mufson E.J. Herrup K. Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer’s disease. J. Neurosci. 2003 23 7 2557 2563 10.1523/JNEUROSCI.23‑07‑02557.2003 12684440
    [Google Scholar]
  70. Su B. Wang X. Nunomura A. Moreira P. Lee H. Perry G. Smith M. Zhu X. Oxidative stress signaling in Alzheimer’s disease. Curr. Alzheimer Res. 2008 5 6 525 532 10.2174/156720508786898451 19075578
    [Google Scholar]
  71. Dong Y. Gu Y. Huan Y. Liu H. Yang S. Traditional Chinese medicine: A potential approach in treating Alzheimer’s disease. J. Alzheimers Dis. 2022 85 2 527 546 34842191
    [Google Scholar]
  72. Calsolaro V. Antognoli R. Okoye C. Monzani F. The use of antipsychotic drugs for treating behavioral symptoms in Alzheimer’s disease. Front. Pharmacol. 2019 10 1465 10.3389/fphar.2019.01465 31920655
    [Google Scholar]
  73. Milenkovic D. Morand C. Cassidy A. Multi-targeted actions of polyphenols in Alzheimer’s disease. Nutr. Aging 2015 3 1 89 99
    [Google Scholar]
  74. Burke S.L. O’Driscoll J. Alcide A. Li T. Moderating risk of Alzheimer’s disease through the use of anxiolytic agents. Int. J. Geriatr. Psychiatry 2017 32 12 1312 1321 10.1002/gps.4614 27805724
    [Google Scholar]
  75. Tariot P.N. Loy R. Ryan J.M. Porsteinsson A. Ismail S. Mood stabilizers in Alzheimer’s disease: Symptomatic and neuroprotective rationales. Adv. Drug Deliv. Rev. 2002 54 12 1567 1577 10.1016/S0169‑409X(02)00153‑9 12453674
    [Google Scholar]
  76. Sun J. Xu J. Wang C. Natural polyphenols for treatment of Alzheimer’s disease. Nutrients 2022 14 9 1957 35565923
    [Google Scholar]
  77. Braidy N. Matin A. Rossi F. Therapeutic approaches to modulating oxidative stress in Alzheimer’s disease: The role of natural antioxidants. Aging Dis. 2017 8 5 516 529
    [Google Scholar]
  78. Balasubramanian P. Seshadri G. Shanmugam M.M. Natural bioactive compounds against Alzheimer’s disease: Their mechanisms and therapeutic potential. Neurosci. Lett. 2019 691 105 111
    [Google Scholar]
  79. Nehru B. Bhalla P. Herbal medicines in the treatment of Alzheimer’s disease. Curr. Drug Targets 2015 16 4 317 329
    [Google Scholar]
  80. Choi S.H. Kim Y.H. Quach T.V. Pomegranate extract alleviates cognitive and behavioral symptoms of Alzheimer’s disease. Sci. Rep. 2020 10 1 10101 32572139
    [Google Scholar]
  81. Kumar G.P. Khanum F. Neuroprotective potential of phytochemicals. Pharmacogn. Rev. 2012 6 12 81 90 10.4103/0973‑7847.99898 23055633
    [Google Scholar]
  82. Cummings J. Ritter A. Zhong K. Clinical trials for disease-modifying therapies in alzheimer’s disease: A primer, lessons learned, and a blueprint for the future. J. Alzheimers Dis. 2018 64 s1 S3 S22 10.3233/JAD‑179901 29562511
    [Google Scholar]
  83. Patil S.P. Gupta V. Mohanty S. Natural products in Alzheimer’s disease therapy: An updated review. Nutr. Neurosci. 2021 24 9 715 732
    [Google Scholar]
  84. Fan R. Xu F. Wang Y. Antioxidant and anti-inflammatory effects of curcumin in treating Alzheimer’s disease: From molecular mechanisms to clinical practice. Neural Regen. Res. 2021 16 2 363 374
    [Google Scholar]
  85. Knopman D.S. Lecanemab reduces brain amyloid-β and delays cognitive worsening. Cell Rep. Med. 2023 4 3 100982 10.1016/j.xcrm.2023.100982 36948153
    [Google Scholar]
  86. Rashad A. Rasool A. Shaheryar M. Sarfraz A. Sarfraz Z. Robles-Velasco K. Cherrez-Ojeda I. Donanemab for Alzheimer’s disease: A systematic review of clinical trials. Healthcare 2022 11 1 32 39 10.3390/healthcare11010032 36611492
    [Google Scholar]
  87. van Dyck C.H. Swanson C.J. Aisen P. Bateman R.J. Chen C. Gee M. Kanekiyo M. Li D. Reyderman L. Cohen S. Froelich L. Katayama S. Sabbagh M. Vellas B. Watson D. Dhadda S. Irizarry M. Kramer L.D. Iwatsubo T. Lecanemab in early Alzheimer’s disease. N. Engl. J. Med. 2023 388 1 9 21 10.1056/NEJMoa2212948 36449413
    [Google Scholar]
  88. Higdon J.V. Frei B. Tea catechins and polyphenols: Health effects, metabolism, and antioxidant functions. Crit. Rev. Food Sci. Nutr. 2003 43 1 89 143 10.1080/10408690390826464 12587987
    [Google Scholar]
  89. Imbimbo B. Balducci C. Ippati S. Watling M. Initial failures of anti-tau antibodies in Alzheimer’s disease are reminiscent of the amyloid-β story. Neural Regen. Res. 2023 18 1 117 118 10.4103/1673‑5374.340409 35799522
    [Google Scholar]
  90. Albani D. Polito L. Natural products for neurodegenerative diseases: Potential therapy for Alzheimer’s disease and future prospects. Neurosci. Lett. 2020 741 135491
    [Google Scholar]
  91. Liu P. Wang Y. Sun Y. Peng G. Neuroinflammation as a potential therapeutic target in Alzheimer’s disease. Clin. Interv. Aging 2022 17 665 674 10.2147/CIA.S357558 35520949
    [Google Scholar]
  92. Loizzo M.R. Tundis R. Menichini F. Natural products and Alzheimer’s disease: Recent progress and future perspectives. Curr. Med. Chem. 2013 20 26 3061 3085
    [Google Scholar]
  93. Tejera D. Mercan D. Sanchez-Caro J.M. Hanan M. Greenberg D. Soreq H. Latz E. Golenbock D. Heneka M.T. Systemic inflammation impairs microglial Aβ clearance through NLRP 3 inflammasome. EMBO J. 2019 38 17 e101064 10.15252/embj.2018101064 31359456
    [Google Scholar]
  94. Butterfield D.A. Swomley A.M. Sultana R. Amyloid β-peptide (1-42)-induced oxidative stress in Alzheimer disease: Importance in disease pathogenesis and progression. Antioxid. Redox Signal. 2013 19 8 823 835 10.1089/ars.2012.5027 23249141
    [Google Scholar]
  95. Vassar R. Kovacs D.M. Yan R. Wong P.C. The beta-secretase enzyme BACE in health and Alzheimer’s disease: Regulation, cell biology, function, and therapeutic potential. J. Neurosci. 2009 29 41 12787 12794 10.1523/JNEUROSCI.3657‑09.2009 19828790
    [Google Scholar]
  96. Subedi L. Gaire B.P. Recent advances in neuroprotective potentials of flavonoids. Future Med. Chem. 2021 13 5 453 477
    [Google Scholar]
  97. Khoury R. Grysman N. Gold J. Patel K. Grossberg G.T. The role of 5 HT6-receptor antagonists in Alzheimer’s disease: An update. Expert Opin. Investig. Drugs 2018 27 6 523 533 10.1080/13543784.2018.1483334 29848076
    [Google Scholar]
  98. Singh M. Kaur M. Kukreja H. Promising phytochemicals for treatment of Alzheimer’s disease. Curr. Pharm. Des. 2016 22 1 209 228
    [Google Scholar]
  99. Lourenço S.C. Moldão-Martins M. Alves V.D. Antioxidants of natural plant origins: From sources to food industry applications. Molecules 2019 24 22 4132 4139 10.3390/molecules24224132 31731614
    [Google Scholar]
  100. Behl T. Kaur I. Aleya L. Unfolding the neuroprotective facets of quercetin in Alzheimer’s disease. Front. Biosci. 2021 26 659 674
    [Google Scholar]
  101. Spencer J.P.E. Flavonoids and brain health: Multiple effects underpinned by common mechanisms. Genes Nutr. 2009 4 4 243 250 10.1007/s12263‑009‑0136‑3 19685255
    [Google Scholar]
  102. Howes M.J.R. Perry N.S.L. Houghton P.J. Plants with traditional uses and activities, relevant to the management of Alzheimer’s disease and other cognitive disorders. Phytother. Res. 2003 17 1 1 18 10.1002/ptr.1280 12557240
    [Google Scholar]
  103. Pluta R. Ułamek-Kozioł M. Januszewski S. Czuczwar S.J. Gut microbiota and pro/prebiotics in Alzheimer’s disease. Aging 2020 12 6 5539 5550 10.18632/aging.102930 32191919
    [Google Scholar]
  104. Deng M. Yan W. Gu Z. Li Y. Chen L. He B. Anti-neuroinflammatory potential of natural products in the treatment of Alzheimer’s disease. Molecules 2023 28 3 1486 10.3390/molecules28031486 36771152
    [Google Scholar]
  105. Gao L. Yuan F. Gao Y. Pterostilbene reduces amyloid-β levels and improves cognitive function in a murine model of Alzheimer’s disease. J. Nutr. Biochem. 2019 64 26 32
    [Google Scholar]
  106. Aggarwal B.B. Harikumar K.B. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int. J. Biochem. Cell Biol. 2009 41 1 40 59 10.1016/j.biocel.2008.06.010 18662800
    [Google Scholar]
  107. Ali B.H. Blunden G. Tanira M.O. Nemmar A. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): A review of recent research. Food Chem. Toxicol. 2008 46 2 409 420 10.1016/j.fct.2007.09.085 17950516
    [Google Scholar]
  108. Reay J.L. Kennedy D.O. Scholey A.B. Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity. J. Psychopharmacol. 2005 19 4 357 365 10.1177/0269881105053286 15982990
    [Google Scholar]
  109. Perry N.B. Burgess E.J. Glennie V. Echinacea standardization: Analytical methods for phenolic compounds and typical levels in medicinal species. J. Agric. Food Chem. 2001 49 4 1702 1706 10.1021/jf001331y 11308313
    [Google Scholar]
  110. Banerjee S.K. Maulik S.K. Effect of garlic on cardiovascular disorders: A review. Nutr. J. 2002 1 1 4 10.1186/1475‑2891‑1‑4 12537594
    [Google Scholar]
  111. Baur J.A. Sinclair D.A. Therapeutic potential of resveratrol: The in vivo evidence. Nat. Rev. Drug Discov. 2006 5 6 493 506 10.1038/nrd2060 16732220
    [Google Scholar]
  112. Zhai Y. Guo X. Apigenin induces apoptosis in HepG2 cells: Involvement of p53 pathway. Toxicol. Lett. 2007 176 3 169 177
    [Google Scholar]
  113. Walker A.F. Marakis G. Simpson E. Hope J.L. Robinson P.A. Hassanein M. Simpson H.C. Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: A randomised controlled trial. Br. J. Gen. Pract. 2006 56 527 437 443 16762125
    [Google Scholar]
  114. Pradhan S.C. Girish C. Hepatoprotective herbal drug, silymarin from Silybum marianum (L.) Gaertn. Therap. Adv. Gastroenterol. 2006 5 2 241 253
    [Google Scholar]
  115. Abd El-Ghani M.M. Traditional medicinal plants of Nigeria: An overview. Agric. Biol. J. N. Am. 2016 7 5 220 247
    [Google Scholar]
  116. Ahmed S. Khan R.A. Jahan N. Khan A.A. Medicinal plants and their role in the wound healing process: A review. Pak. J. Biol. Sci. 2016 19 1 1 10 26930795
    [Google Scholar]
  117. Dias D.A. Urban S. Roessner U. A historical overview of natural products in drug discovery. Metabolites 2012 2 2 303 336 10.3390/metabo2020303 24957513
    [Google Scholar]
  118. Grabska-Kobyłecka I. Szpakowski P. Król A. Książek-Winiarek D. Kobyłecki A. Głąbiński A. Nowak D. Polyphenols and their impact on the prevention of neurodegenerative diseases and development. Nutrients 2023 15 15 3454 3488 10.3390/nu15153454 37571391
    [Google Scholar]
  119. Sharifi-Rad J. Rapposelli S. Sestito S. Herrera-Bravo J. Arancibia-Diaz A. Salazar L.A. Yeskaliyeva B. Beyatli A. Leyva-Gómez G. González-Contreras C. Gürer E.S. Martorell M. Calina D. Multi-target mechanisms of phytochemicals in Alzheimer’s disease: Effects on oxidative stress, neuroinflammation and protein aggregation. J. Pers. Med. 2022 12 9 1515 10.3390/jpm12091515 36143299
    [Google Scholar]
  120. Zhang X.W. Chen J.Y. Ouyang D. Lu J.H. Quercetin in animal models of Alzheimer’s disease: A systematic review of preclinical studies. Int. J. Mol. Sci. 2020 21 2 493 499 10.3390/ijms21020493 31941000
    [Google Scholar]
  121. Gertsch J. How scientific is the science in ethnopharmacology? Historical perspectives and epistemological problems. J. Ethnopharmacol. 2009 122 2 177 183 10.1016/j.jep.2009.01.010 19185054
    [Google Scholar]
  122. Pan S.Y. Zhou S.F. Gao S.H. Yu Z.L. Zhang S.F. Tang M.K. Sun J.N. Ma D.L. Han Y.F. Fong W.F. Ko K.M. New perspectives on how to discover drugs from herbal medicines: CAM’s outstanding contribution to modern therapeutics. Evid. Based Complement. Alternat. Med. 2013 2013 1 25 10.1155/2013/627375 23634172
    [Google Scholar]
  123. Ghorbani A. Esmaeilizadeh M. Pharmacological properties of Salvia officinalis and its components. J. Tradit. Complement. Med. 2017 7 4 433 440 10.1016/j.jtcme.2016.12.014 29034191
    [Google Scholar]
  124. Grienke U. Silke J. Tasdemir D. Bioactive compounds from marine and freshwater microalgae: The potential for industrial applications. Mol. Nutr. Food Res. 2014 58 3 837 852
    [Google Scholar]
  125. Yoo K.Y. Park S.Y. Terpenoids as potential anti-Alzheimer’s disease therapeutics. Molecules 2012 17 3 3524 3538 10.3390/molecules17033524 22430119
    [Google Scholar]
  126. Karamian R. Asadbegy M. Antioxidant, anti-inflammatory, and neuroprotective properties of flavonoids extracted from medicinal plants: A mechanistic review. J. Ethnopharmacol. 2019 232 385 398
    [Google Scholar]
  127. Nawaz H. Shad M.A. Rehman N. Ullah N. Phytochemical screening, anti-inflammatory and antioxidant potential of extracts of Berberis lycium. Pak. J. Pharm. Sci. 2019 32 3 1209 1215 31278715
    [Google Scholar]
  128. Shah H. Dehghani F. Ramezan M. Gannaban R.B. Haque Z.F. Rahimi F. Abbasi S. Shin A.C. Revisiting the role of vitamins and minerals in Alzheimer’s disease. Antioxidants 2023 12 2 415 10.3390/antiox12020415 36829974
    [Google Scholar]
  129. Heinrich M. Barnes J. Gibbons S. Williamson E.M. Fundamentals of pharmacognosy and phytotherapy. Elsevier Health Sciences 2012
    [Google Scholar]
  130. Basheer A. Agarwal A. Mishra B. Gupta A. Padma Srivastava M.V. Kirubakaran R. Vishnu V. Use of Bacopa monnieri in the treatment of dementia due to Alzheimer disease: Systematic review of randomized controlled trials. Interact. J. Med. Res. 2022 11 2 e38542 10.2196/38542 35612544
    [Google Scholar]
  131. Mikulska P. Malinowska M. Ignacyk M. Szustowski P. Nowak J. Pesta K. Szeląg M. Szklanny D. Judasz E. Kaczmarek G. Ejiohuo O.P. Paczkowska-Walendowska M. Gościniak A. Cielecka-Piontek J. Ashwagandha (Withania somnifera)—current research on the health-promoting activities: A narrative review. Pharmaceutics 2023 15 4 1057 10.3390/pharmaceutics15041057 37111543
    [Google Scholar]
  132. Huang W.Y. Cai Y.Z. Zhang Y. Natural phenolic compounds from medicinal herbs and dietary plants: Potential use for cancer prevention. Nutr. Cancer 2009 62 1 1 20 10.1080/01635580903191585 20043255
    [Google Scholar]
  133. Zhou Y. Xie W. Li Y. Mechanisms and therapeutic potential of herbal drugs and natural compounds for the treatment of rheumatoid arthritis. Front. Pharmacol. 2021 12 685757
    [Google Scholar]
  134. Santos L.L. Oliveira R.D. Figueiredo J.A. Medicinal plants and natural compounds as potential agents for the treatment of Alzheimer’s disease. Curr. Alzheimer Res. 2018 15 8 634 648
    [Google Scholar]
  135. Nalivaeva N.N. Turner A.J. Inhibitors of acetylcholinesterase in the treatment of Alzheimer’s disease: Progress and prospects. Eur. J. Pharmacol. 2019 857 172456
    [Google Scholar]
  136. Imbimbo B.P. Lombard J. Pomara N. Pathophysiology of Alzheimer’s disease. Neuroimaging Clin. N. Am. 2005 15 4 727 753, ix 10.1016/j.nic.2005.09.009 16443487
    [Google Scholar]
  137. Grossberg G.T. Tong G. Burke A.D. Tariot P.N. Present algorithms and future treatments for Alzheimer’s disease. J. Alzheimers Dis. 2019 67 4 1157 1171 10.3233/JAD‑180903 30741683
    [Google Scholar]
  138. Anand R Gill KD Mahdi AA Therapeutics of Alzheimer's disease: Past, present and future. Neuropharmacology 2014 76 Pt A 27 50
    [Google Scholar]
  139. Parsons C.G. Stoffler A. Danysz W. Memantine: A NMDA receptor antagonist that improves memory and learning. Pharmacol. Biochem. Behav. 2007 86 4 385 399 17915302
    [Google Scholar]
  140. Doody R.S. Raman R. Farlow M. Iwatsubo T. Vellas B. Joffe S. Kieburtz K. He F. Sun X. Thomas R.G. Aisen P.S. Siemers E. Sethuraman G. Mohs R. A phase 3 trial of semagacestat for treatment of Alzheimer’s disease. N. Engl. J. Med. 2013 369 4 341 350 10.1056/NEJMoa1210951 23883379
    [Google Scholar]
  141. Coric V. van Dyck C.H. Salloway S. Andreasen N. Brody M. Richter R.W. Soininen H. Thein S. Shiovitz T. Pilcher G. Colby S. Rollin L. Dockens R. Pachai C. Portelius E. Andreasson U. Blennow K. Soares H. Albright C. Feldman H.H. Berman R.M. Safety and tolerability of the γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch. Neurol. 2012 69 11 1430 1440 10.1001/archneurol.2012.2194 22892585
    [Google Scholar]
  142. Wilcock G.K. Black S.E. Hendrix S.B. Zavitz K.H. Swabb E.A. Laughlin M.A. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer’s disease: A randomised phase II trial. Lancet Neurol. 2008 7 6 483 493 10.1016/S1474‑4422(08)70090‑5 18450517
    [Google Scholar]
  143. Egan M.F. Kost J. Tariot P.N. Aisen P.S. Cummings J.L. Vellas B. Sur C. Mukai Y. Voss T. Furtek C. Mahoney E. Harper Mozley L. Vandenberghe R. Mo Y. Michelson D. Randomized trial of verubecestat for mild-to-moderate Alzheimer’s disease. N. Engl. J. Med. 2018 378 18 1691 1703 10.1056/NEJMoa1706441 29719179
    [Google Scholar]
  144. Honig L.S. Vellas B. Woodward M. Boada M. Bullock R. Borrie M. Hager K. Andreasen N. Scarpini E. Liu-Seifert H. Case M. Dean R.A. Hake A. Sundell K. Poole Hoffmann V. Carlson C. Khanna R. Mintun M. DeMattos R. Selzler K.J. Siemers E. Trial of solanezumab for mild dementia due to Alzheimer’s disease. N. Engl. J. Med. 2018 378 4 321 330 10.1056/NEJMoa1705971 29365294
    [Google Scholar]
  145. Wessels A.M. Tariot P.N. Zimmer J.A. Selzler K.J. Bragg S.M. Andersen S.W. Landry J. Krull J.H. Downing A.M. Willis B.A. Shcherbinin S. Mullen J. Barker P. Schumi J. Shering C. Matthews B.R. Stern R.A. Vellas B. Cohen S. MacSweeney E. Boada M. Sims J.R. Efficacy and safety of lanabecestat for treatment of early and mild Alzheimer’s disease: The AMARANTH and DAYBREAK-ALZ randomized clinical trials. JAMA Neurol. 2020 77 2 199 209 10.1001/jamaneurol.2019.3988 31764959
    [Google Scholar]
  146. Sevigny J. Chiao P. Bussière T. Weinreb P.H. Williams L. Maier M. Dunstan R. Salloway S. Chen T. Ling Y. O’Gorman J. Qian F. Arastu M. Li M. Chollate S. Brennan M.S. Quintero-Monzon O. Scannevin R.H. Arnold H.M. Engber T. Rhodes K. Ferrero J. Hang Y. Mikulskis A. Grimm J. Hock C. Nitsch R.M. Sandrock A. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature 2016 537 7618 50 56 10.1038/nature19323 27582220
    [Google Scholar]
  147. Ostrowitzki S. Lasser R.A. Dorflinger E. Scheltens P. Barkhof F. Nikolcheva T. Ashford E. Retout S. Hofmann C. Delmar P. Klein G. Andjelkovic M. Dubois B. Boada M. Blennow K. Santarelli L. Fontoura P. A phase III randomized trial of gantenerumab in prodromal Alzheimer’s disease. Alzheimers Res. Ther. 2017 9 1 95 10.1186/s13195‑017‑0318‑y 29221491
    [Google Scholar]
  148. Swanson C.J. Zhang Y. Dhadda S. A phase 2 randomized trial of BAN2401 in early Alzheimer’s disease. Alzheimers Res. Ther. 2021 13 1 80 10.1186/s13195‑021‑00813‑8 33865446
    [Google Scholar]
  149. Gauthier S. Feldman H.H. Schneider L.S. Wilcock G.K. Frisoni G.B. Hardlund J.H. Moebius H.J. Bentham P. Kook K.A. Wischik D.J. Schelter B.O. Davis C.S. Staff R.T. Bracoud L. Shamsi K. Storey J.M.D. Harrington C.R. Wischik C.M. Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer’s disease: A randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet 2016 388 10062 2873 2884 10.1016/S0140‑6736(16)31275‑2 27863809
    [Google Scholar]
  150. Bakker A. Albert M.S. Krauss G.L. Response of memory networks to low-dose levetiracetam in mild cognitive impairment: A randomized, controlled study. Neuroimage 2015 23 146 154
    [Google Scholar]
  151. Deane R. Singh I. Sagare A.P. Bell R.D. Ross N.T. LaRue B. Love R. Perry S. Paquette N. Deane R.J. Thiyagarajan M. Zarcone T. Fritz G. Friedman A.E. Miller B.L. Zlokovic B.V. A multimodal RAGE-specific inhibitor reduces amyloid β–mediated brain disorder in a mouse model of Alzheimer disease. J. Clin. Invest. 2012 122 4 1377 1392 10.1172/JCI58642 22406537
    [Google Scholar]
  152. Wightman E.L. Reay J.L. Kennedy D.O. Effects of glutamate modulation on cognitive function in Alzheimer’s disease: Review and potential therapies. Neurosci. Biobehav. Rev. 2019 102 171 185
    [Google Scholar]
  153. Piette F. Belmin J. Vincent H. Masitinib as an add-on therapy for mild to moderate Alzheimer’s disease: A randomized, placebo-controlled trial. Alzheimers Dement. 2017 13 4 357 365
    [Google Scholar]
  154. Wischik C.M. Staff R.T. Wischik D.J. Bentham P. Murray A.D. Storey J.M.D. Kook K.A. Harrington C.R. Tau aggregation inhibitor therapy: An exploratory phase 2 study in mild or moderate Alzheimer’s disease. J. Alzheimers Dis. 2015 44 2 705 720 10.3233/JAD‑142874 25550228
    [Google Scholar]
  155. Medina M. Avila J. The need for better AD animal models. Front. Pharmacol. 2014 5 227 236 10.3389/fphar.2014.00227 25386142
    [Google Scholar]
  156. Kaufman A.C. Salazar S.V. Haas L.T. Yang J. Kostylev M.A. Jeng A.T. Robinson S.A. Gunther E.C. van Dyck C.H. Nygaard H.B. Strittmatter S.M. F yn inhibition rescues established memory and synapse loss in A lzheimer mice. Ann. Neurol. 2015 77 6 953 971 10.1002/ana.24394 25707991
    [Google Scholar]
  157. Takaya Y. Kuwabara M. Takiguchi Y. Mizoribine inhibits the protein folding activity of heat shock protein 60. PLoS One 2014 9 9 1 11
    [Google Scholar]
  158. Young J.C. Hartl F.U. Molecular chaperones: Hsp60 and Hsp70 families in protein folding and degradation. Protein Pept. Lett. 2003 10 4 343 352
    [Google Scholar]
  159. Dougherty P.G. Sahni A. Pei D. Understanding the binding modes of avrainvillamideanalogs to Hsp60. J. Med. Chem. 2020 63 21 12696 12705 33073986
    [Google Scholar]
  160. Fukumoto K. Saito S. Inoue M. Structure-activity relationship studies on epolactaene derivatives as inhibitors of heat shock protein 60. J. Med. Chem. 2015 58 15 6097 6108
    [Google Scholar]
  161. Boland B. Kumar A. Lee S. Platt F.M. Modulation of autophagy as a therapeutic target for Alzheimer’s disease. Trends Mol. Med. 2018 24 7 515 534
    [Google Scholar]
  162. Liu R. Meng Y. Wu J. YM-01, an Hsp70 inhibitor, reduces tau pathology in a mouse model of Alzheimer’s disease. Neurobiol. Aging 2019 81 195 206
    [Google Scholar]
  163. Jinwal U.K. Miyata Y. Koren J. Chemical manipulation of Hsp90 as a novel treatment strategy for tauopathies. Neuron 2009 63 3 260 272
    [Google Scholar]
  164. Gehring U. Bursell J. Feige U. Geldanamycin inhibits the tau phosphorylation pathway by destabilizing Hsp90. J. Biol. Chem. 2002 277 6 4506 4512
    [Google Scholar]
  165. Samant R.S. Clarke P.A. Workman P. 17-AAG inhibits Hsp90, reducing tau phosphorylation. Cancer Lett. 2016 370 2 209 217 26965998
    [Google Scholar]
  166. Biebl M.M. Buchner J. Structure, function, and regulation of the Hsp90 machinery. Cold Spring Harb. Perspect. Biol. 2019 11 9 a034017 10.1101/cshperspect.a034017 30745292
    [Google Scholar]
/content/journals/car/10.2174/0115672050361294241211071813
Loading
Recent Updates on Alzheimer’s Disease: Pathogenesis, Pathophysiology, Molecular Approaches and Natural Bioactive Compounds Used in Contemporary Time to Alleviate Disease
Bentham Science Publishers ; https://doi.org/10.2174/0115672050361294241211071813
/content/journals/car/10.2174/0115672050361294241211071813
/content/journals/car/10.2174/0115672050361294241211071813
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: neurofibrillary tangles ; decline of memory ; Alzheimer's disease ; Bioactive compounds ; amyloid-beta peptide

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