Prince M, Albanese E, Guerchet M, Prina M World Alzheimer Report 2014: Dementia and Risk Reduction—An analysis of protective and modifiable risk factors. Alzheimer’s Disease International, London, 2014.

Alzheimer’s Association. 2023 Alzheimer’s disease facts and figures. Alzheimers Dement. 2023;19:1598–695. https://doi.org/10.1002/alz.13016.

Article  Google Scholar 

Kumaran KR, Yunusa S, Perimal EK, Wahab H, Müller CP, Hassan Z. Insights into the pathophysiology of Alzheimer’s disease and potential therapeutic targets: a current perspective. J Alzheimers Dis. 2023;91:507–30.

Article  Google Scholar 

Yang Y, Lina Q. Research progress on the pathogenesis, diagnosis, and drug therapy of Alzheimer’s disease. Brain Sci. 2024;16:590. https://doi.org/10.3390/brainsci14060590.

Article  CAS  Google Scholar 

van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388:9–21.

Article  PubMed  Google Scholar 

Giacobini E, Cuello AC, Fisher A. Reimagining cholinergic therapy for Alzheimer’s disease. Brain. 2022;145:22350–2275.

Article  Google Scholar 

Sharma A, Rudrawar S, Bharate SB, Jadhav HR. Recent advancements in the therapeutic approaches for Alzheimer’s disease treatment: current and future perspective. RSC Med Chem. 2025;16:652–93.

Article  CAS  PubMed  Google Scholar 

Darvesh S, Hopkins DA, Geula C. Neurobiology of butyrylcholinesterase. Nat Rev Neurosci. 2003;4:131–8.

Article  CAS  PubMed  Google Scholar 

Mesulam MM, Geula C. Systematic regional variations in the loss of cortical cholinergic fibers in Alzheimer’s disease. Cereb Cortex. 1996;6:165–77.

Article  PubMed  Google Scholar 

Mesulam MM, Geula C, Morán MA. Anatomy of cholinesterase inhibition in Alzheimer’s disease: effect of physostigmine and tetrahydroaminoacridine on plaques and tangles. Ann Neurol. 1987;22:683–91.

Article  CAS  PubMed  Google Scholar 

Yoo J, Lee J, Ahn B, Han J, Lim MH. Multi-target-directed therapeutic strategies for Alzheimer’s disease: controlling amyloid-β aggregation, metal ion homeostasis, and enzyme inhibition. Chem Sci. 2025;16:2105–35.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nie Y, Chu C, Qin Q, Shen H, Wen L, Tang Y, et al. Lipid metabolism and oxidative stress in patients with Alzheimer’s disease and amnestic mild cognitive impairment. Brain Pathol. 2024;34:e13202.

Article  CAS  PubMed  Google Scholar 

Perluigi M, Di Domenico F, Butterfield DA. Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer disease. Physiol Rev. 2024;104:103–97.

Article  CAS  PubMed  Google Scholar 

Yin F. Lipid metabolism and Alzheimer’s disease: clinical evidence, mechanistic link and therapeutic promise. FEBS J. 2023;290:1420–53.

Article  CAS  PubMed  Google Scholar 

Viayna E, Coquelle N, Cieslikiewicz-Bouet M, Cisternas P, Oliva CA, Sánchez-López E, et al. Discovery of a potent dual inhibitor of acetylcholinesterase and butyrylcholinesterase with antioxidant activity that alleviates Alzheimer-like pathology in old APP/PS1 mice. J Med Chem. 2021;64:812–39.

Article  CAS  PubMed  Google Scholar 

Reid GA, Chilukuri N, Darvesh S. Butyrylcholinesterase and the cholinergic system. Neuroscience. 2013;234:53–68.

Article  CAS  PubMed  Google Scholar 

Varadharajan A, Davis AD, Ghosh A, Jagtap T, Xavier A, Menon AJ, et al. Guidelines for pharmacotherapy in Alzheimer’s disease – a primer on FDA-approved drugs. J Neurosci Rural Pr. 2023;14:566–73.

Article  Google Scholar 

Lam B, Masellis M, Freedman M, Stuss DT, Black SE. Cholinesterase inhibitors in Alzheimer’s disease and Lewy body spectrum disorders: the emerging pharmacogenetic story. Hum Genomics. 2009;4:91–106.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Greig NH, Lahiri DK, Sambamurti K. Butyrylcholinesterase: an important new target in Alzheimer’s disease therapy. Int Psychogeriatr. 2002;14:77–91.

Article  PubMed  Google Scholar 

Elsawalhy M, Abdel-Rahman AA, Basiony EA, Ellithy SA, Hassan AA, Abou-Amra ES, et al. Novel dual acetyl- and butyrylcholinesterase inhibitors based on the pyridyl-pyridazine moiety for the potential treatment of Alzheimer’s disease. Pharmaceuticals (Basel). 2024;17:1407.

Article  CAS  PubMed  Google Scholar 

Jiang CS, Ge YX, Cheng ZQ, Wang YY, Tao HR, Zhu K, et al. Discovery of new selective butyrylcholinesterase (BChE) inhibitors with anti-Aβ aggregation activity: structure-based virtual screening, hit optimization and biological evaluation. Molecules. 2019;24:2568.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Darvesh S. Butyrylcholinesterase as a diagnostic and therapeutic target for Alzheimer’s disease. Curr Alzheimer Res. 2016;13:1173–7.

Article  CAS  PubMed  Google Scholar 

Zhou S, Yuan Y, Zheng F, Zhan CG. Structure-based virtual screening leading to discovery of highly selective butyrylcholinesterase inhibitors with solanaceous alkaloid scaffolds. Chem Biol Interact. 2019;308:372–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bolognesi ML, Bartolini M, Cavalli A, Andrisano V, Rosini M, Minarini A. Design, synthesis, and biological evaluation of conformationally restricted rivastigmine analogues. J Med Chem. 2004;47:5945–52.

Article  CAS  PubMed  Google Scholar 

Darras FH, Kling B, Heilmann J, Decker M. Neuroprotective tri- and tetracyclic BChE inhibitors releasing reversible inhibitors upon carbamate transfer. ACS Med Chem Lett. 2012;3:914–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mohamed LW, El-Yamany MF. Design and synthesis of novel 1,4-benzodiazepine derivatives and their biological evaluation as cholinesterase inhibitors. Arch Pharm Res. 2012;35:1369–77.

Article  CAS  PubMed  Google Scholar 

Craig LA, Hong NS, McDonald RJ. Revisiting the cholinergic hypothesis in the development of Alzheimer’s disease. Neurosci Biobehav Rev. 2011;35:1397–409.

Article  CAS  PubMed  Google Scholar 

Smith SG, Sanchez R, Zhou MM. Privileged diazepine compounds and their emergence as bromodomain inhibitors. Chem Biol. 2014;21:573–83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ellman GL, Courtney KD, Andres V Jr, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharm. 1961;7:88–95.

Article  CAS  PubMed  Google Scholar 

Darras FH, Pockes S, Huang G, Wehle S, Strasser A, Wittmann H-J, et al. Synthesis, biological evaluation, and computational studies of tri- and tetracyclic nitrogen-bridgehead compounds as potent dual-acting AChE inhibitors and hH3 receptor antagonists. ACS Chem Neurosci. 2014;5:225–42.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Amitai G, Moorad D, Adani R, Doctor BP. Inhibition of acetylcholinesterase and butyrylcholinesterase by chlorpyrifos-oxon. Biochem Pharm. 1998;56:293–9.

Article  CAS  PubMed  Google Scholar 

Pidany F, Kroustkova J, Al Mamun A, Suchankova D, Brazzolotto X, Nachon F, et al. Highly selective butyrylcholinesterase inhibitors related to Amaryllidaceae alkaloids: design, synthesis, and biological evaluation. Eur J Med Chem. 2023;252:115301.

Article  CAS  PubMed  Google Scholar 

Hoffmann M, Stiller C, Endres E, Scheiner M, Gunesch S, Sotriffer C, et al. Highly