Neuropharmacological perspectives on Alzheimer’s disease

Authors

  • Natalia Moningka Sandip Institute of Pharmaceutical Sciences, Nashik, Maharashtra, India
  • Orbanus Naharia Sandip Institute of Pharmaceutical Sciences, Nashik, Maharashtra, India
  • Anatje Lihiang Sandip Institute of Pharmaceutical Sciences, Nashik, Maharashtra, India

Keywords:

Alzheimer’s disease, Acetyl cholinesterase inhibitors, Neuropharmacological, Pharmacotherapeutic

Abstract

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders, characterized by the progressive loss of nerve cells across various regions of the brain. Pathologically, it is associated with intracellular neurofibrillary tangles and extracellular amyloid protein deposits, which disrupt neural transmission and lead to cognitive decline. Nutrition and lifestyle factors play a crucial role in both the development and prevention of AD. Early diagnosis relies on sensitive biomarkers capable of distinguishing between different causes of dementia. Emerging therapeutic strategies, including the use of induced pluripotent stem cells, show promise in addressing the underlying pathology. The primary hypotheses explaining AD pathogenesis include the cholinergic, tau, and amyloid hypotheses, with additional risk factors such as age, genetics, head trauma, vascular diseases, infections, and environmental influences. Currently approved pharmacotherapies—cholinesterase inhibitors and NMDA receptor antagonists—alleviate symptoms but do not cure or prevent disease progression. Contemporary research focuses on multiple pathological processes, including tau protein dysregulation, β-amyloid accumulation, oxidative stress, neuroinflammation, and cholinergic dysfunction, aiming to develop disease-modifying treatments. This review provides a comprehensive neuropharmacological perspective on AD, emphasizing the underlying mechanisms, risk factors, and current and emerging pharmacotherapeutic strategies for its management.

References

Kumar K, Kumar A, Keegan RM, Deshmukh R. Recent advances in the neurobiology and neuropharmacology of Alzheimer’s disease. Biomed Pharmacother. 2018;98:297–307.

Gilles C, Ertlé S. Pharmacological models in Alzheimer's disease research. Dialogues Clin Neurosci. 2000 Sep;2(3):247–55.

Massoud F, Gauthier S. Update on the pharmacological treatment of Alzheimer’s disease. Curr Neuropharmacol. 2010 Mar;8(1):69–80.

Anand R, Gill KD, Mahdi AA. Therapeutics of Alzheimer's disease: past, present and future. Neuropharmacology. 2014;76(Pt A):27–50.

Rogawski MA, Wenk GL. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev. 2003;9:275–308.

Webber KM, Raina AK, Marlatt MW, Zhu X, Prat MI, Morelli L, et al. The cell cycle in Alzheimer disease: a unique target for neuropharmacology. Mech Ageing Dev. 2005;126(10):1019–25.

Drukarch B, Leysen JE, Stoof JC. Further analysis of the neuropharmacological profile of 9-amino-1,2,3,4-tetrahydroacridine (THA), an alleged drug for the treatment of Alzheimer's disease. Life Sci. 1988;42(9):1011–7.

Nehlig A. The neuroprotective effects of cocoa flavanol and its influence on cognitive performance. Br J Clin Pharmacol. 2013;75(3):716–27.

Sinyor B, Mineo J, Ochner C. Alzheimer's disease, inflammation, and the role of antioxidants. J Alzheimers Dis Rep. 2020;4(1):175–83.

Alzheimer's Association. 2021 Alzheimer's disease facts and figures. Alzheimers Dement. 2021;17:327–406.

Kim JH. Genetics of Alzheimer's disease. Dement Neurocogn Disord. 2018 Dec;17(4):131–6.

Amaducci LA, Rocca WA, Schoenberg BS. Origin of the distinction between Alzheimer's disease and senile dementia. Neurology. 1986 Nov;36(11):1497.

Prince M, Wimo A, Guerchet M, Ali G, Wu Y, Prina M. World Alzheimer Report 2015: the global impact of dementia. London: Alzheimer’s Disease International; 2015. Available from: https://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf

Hosseini L, Mahmoudi J, Pashazadeh F, Salehi-Pourmehr H, Sadigh-Eteghad S. Protective effects of nicotinamide adenine dinucleotide and related precursors in Alzheimer's disease: a systematic review of preclinical studies. J Mol Neurosci. 2021 Apr 28. doi: 10.1007/s12031-021-01842-6

Canadian Study of Health and Aging. Study methods and prevalence of dementia. CMAJ. 1994;150(6):899–913.

Du X, Wang X, Geng M. Alzheimer’s disease hypothesis and related therapies. Transl Neurodegener. 2018;7:2.

Sastre M, Steiner H, Fuchs K, Capell A, Multhaup G, Condron MM, et al. Presenilin-dependent γ-secretase processing of β-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch. EMBO Rep. 2001;2:835–41.

Long JM, Holtzman DM. Alzheimer disease: an update on pathobiology and treatment strategies. Cell. 2019 Oct 3;179(2):312–39.

Sienski G, et al. APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia. Sci Transl Med. 2021 Mar 3;13(583):eaaz4564.

Blennow K, de Leon MJ, Zetterberg H. Alzheimer's disease. Lancet. 2006 Jul 29;368(9533):387–403.

Kim JH. Genetics of Alzheimer's disease. Dement Neurocogn Disord. 2018;17(4):131–6.

Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer’s disease. Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5644–51.

Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science. 1992;256(5054):184–5.

Wang J, Gu B, Masters C, et al. A systemic view of Alzheimer disease—insights from amyloid-β metabolism beyond the brain. Nat Rev Neurol. 2017;13:612–23.

Musiek ES, Holtzman DM. Three dimensions of the amyloid hypothesis: time, space and 'wingmen'. Nat Neurosci. 2015;18:800–6.

Brier MR, Gordon B, Friedrichsen K, McCarthy J, Stern A. Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease. Sci Transl Med. 2016;8(338):338ra66.

Chun W, Johnson GVW. The role of tau phosphorylation and cleavage in neuronal cell death. Front Biosci. 2007;12:733–56.

Hasselmo ME, Anderson BP, Bower JM. Cholinergic modulation of cortical associative memory function. J Neurophysiol. 1992;67(5):1230–46.

Fine A, Hoyle C, Maclean CJ, LeVatte TL, Baker HF, Ridley RM. Learning impairments following injection of a selective cholinergic immunotoxin, ME20.4 IgG-saporin, into the basal nucleus of Meynert in monkeys. Neuroscience. 1997;81(2):331–43.

Summers WK, Viesselman JO, Marsh GM, Candelora K. Use of THA in treatment of Alzheimer-like dementia: pilot study in twelve patients. Biol Psychiatry. 1981 Feb;16(2):145–53.

Fotiou DF, Stergiou V, Tsiptsios D, Lithari C, Nakou M, Karlovasitou A. Cholinergic deficiency in Alzheimer's and Parkinson's disease: evaluation with pupillometry. Int J Psychophysiol. 2009 Aug;73(2):143–9.

Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593.

Van Marum RJ. Update on the use of memantine in Alzheimer's disease. Neuropsychiatr Dis Treat. 2009;5:237–47.

Howard RJ, Juszczak E, Ballard CG, et al. Donepezil for the treatment of agitation in Alzheimer's disease. N Engl J Med. 2007 Oct 4;357(14):1382–92.

Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006;355(15):1525–38.

Bentham P, Gray R, Sellwood E, Raftery J. Effectiveness of rivastigmine in Alzheimer's disease. BMJ. 1999;319(7210):640–1.

DeJong R, Osterlund OW, Roy GE. Measurement of quality of life changes in patients with Alzheimer’s disease. Clin Ther. 1989;11:545–54.

Arnold SE, Hyman BT, Flory J, Damasio AR, Van Hoesen GW. The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. Cereb Cortex. 1991;1(1):103–16.

Chan A, Paskavitz J, Remington R, Rasmussen S, Shea TB. Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer’s disease: a 1-year, open-label pilot study with a 16-month caregiver extension. Am J Alzheimers Dis Other Demen. 2009;23(6):571–85.

Goedert M, et al. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron. 1989;3(4):519–26.

Kelly JP, Filley CM. Proneness to psychological distress is associated with risk of Alzheimer’s disease. Neurology. 2004 Sep;63(5):941.

Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer's disease in a community population of older persons. JAMA. 1989;262(18):2551–6.

Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease. Proc Natl Acad Sci U S A. 2006;103(15):5644–51.

Selkoe DJ, Podlisny MB. Deciphering the genetic basis of Alzheimer's disease. Annu Rev Genomics Hum Genet. 2002;3:67–99.

Ohnishi A, Mihara M, Kamakura H, et al. Comparison of the pharmacokinetics of E2020, a new compound for Alzheimer's disease, in healthy young and elderly subjects. J Clin Pharmacol. 1993;33(11):1086–91.

Scott LJ, Goa KL. Galantamine: a review of its use in Alzheimer's disease. Drugs. 2000;60(5):1095–122.

Hossain M, Jhee SS, Shiovitz T, et al. Estimation of the absolute bioavailability of rivastigmine in patients with mild to moderate dementia of the Alzheimer's type. Clin Pharmacokinet. 2002;41(3):225–34.

Dooley M, Lamb HM. Donepezil: a review of its use in Alzheimer's disease. Drugs Aging. 2000;16(3):199–226. doi: 10.2165/00002512-200016030-00005

Potter PE. Current investigational drugs for treatment of Alzheimer’s disease. Front Clin Drug Res Alzheimer Disord. 2015;4:176–235.

Bhana N, Perry CM. Olanzapine: a review of its use in the treatment of bipolar I disorder. CNS Drugs. 2001;15(11):871–904. doi: 10.2165/00023210-200115110-00005

Bostwick JR, Guthrie SK, Ellingrod VL. Antipsychotic-induced hyperprolactinemia. Pharmacotherapy. 2009 Jan;29(1):64–73. doi: 10.1592/phco.29.1.64

Felder CC. GPCR drug discovery—moving beyond the orthosteric to the allosteric domain. Adv Pharmacol. 2019;86:1–20.

Lilienfeld S. Galantamine—a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS Drug Rev. 2002;8(2):159–76. doi: 10.1111/j.1527-3458.2002.tb00221.x

Carlesimo GA, Oscar-Berman M. Memory deficits in Alzheimer's patients: a comprehensive review. Neuropsychol Rev. 1992;3(2):119–69. doi: 10.1007/BF01108841

Jelicic M, Bonebakker AE, Bonke B. Implicit memory performance of patients with Alzheimer's disease: a brief review. Int Psychogeriatr. 1995;7(3):385–92. doi: 10.1017/S1041610295002134

Förstl H, Kurz A. Clinical features of Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci. 1999;249(6):288–90. doi: 10.1007/s004060050101

Zhou J, Zhang S, Zhao X, Wei T. Melatonin impairs NADPH oxidase assembly and decreases superoxide anion production in microglia exposed to amyloid-beta1-42. J Pineal Res. 2008;45(2):157–65. doi: 10.1111/j.1600-079X.2008.00570.x

Feng Z, Zhang JT. Protective effect of melatonin on beta-amyloid-induced apoptosis in rat astroglioma C6 cells and its mechanism. Free Radic Biol Med. 2004;37(11):1790–801. doi: 10.1016/j.freeradbiomed.2004.08.023.

Downloads

Published

2025-08-06

How to Cite

Moningka, N., Naharia, O., & Lihiang, A. (2025). Neuropharmacological perspectives on Alzheimer’s disease. Advances in Pharmacology Research, 1(2), 01–06. Retrieved from https://www.dzarc.com/Pharma/article/view/736

Issue

Section

Articles