• SWETHA G. Department of Pharmacology, the Oxford College of Pharmacy, Bangalore, Karnataka 560068
  • ANJALI RAJ Department of Pharmacology, the Oxford College of Pharmacy, Bangalore, Karnataka 560068
  • SANIYA TABASSUM Department of Pharmacology, the Oxford College of Pharmacy, Bangalore, Karnataka 560068
  • DOUGLAS ZORINMAWIA CHHAKCHHUAK Department of Pharmacology, the Oxford College of Pharmacy, Bangalore, Karnataka 560068




Oxidative stress, Free radicals, Alzheimer’s disease, Amyloid plaques, Tau proteins, Acetylcholine


Dementia is defined by the debilitation of cognition and behavior of individuals more than 65 y. Alzheimer's disease (AD) is the most pervasive pervasive form of dementia, afflicting around 47 million individuals worldwide. Oxidative damage is a significant component in the pathophysiology of Alzheimer's disease (AD). Assessment of Alzheimer's disease mind has shown a lot of oxidative harm, related with both trademark pathologies (senile plaques and neurofibrillary tangles) just as in typical seeming pyramidal neurons. By the by, the process that eventually causes disruption of redox balance and furthermore the origin of the free radicals are as yet hazy. There is likewise the accessibility of proof that oxidative stress may enhance the conglomeration and production of Aβ and furthermore help the polymerization just as phosphorylation of tau, subsequently making a pernicious cycle that invigorates the development and even commencement of Alzheimer's. These neurotic trademarks have complex proportional collaborations with cholinergic abrasions. This review may give complemental data for understanding the relationship between oxidative stress, amyloid plaques, tau proteins and cholinergic system in processing of AD.


Download data is not yet available.


DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener. 2019 Dec;14(1):32. doi: 10.1186/s13024-019-0333-5, PMID 31375134.

Kumar A, Singh A, Ekavali. A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacol Rep. 2015 Apr 1;67(2):195-203. doi: 10.1016/j.pharep.2014.09.004, PMID 25712639.

Kumar Thakur A, Kamboj P, Goswami K, Ahuja K. Pathophysiology and management of alzheimer’s disease: an overview. JAPLR;7(2). doi: 10.15406/japlr.2018.07.00230.

Guo T, Zhang D, Zeng Y, Huang TY, Xu H, Zhao Y. Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease. Mol Neurodegener. 2020 Dec;15(1):40. doi: 10.1186/s13024-020-00391-7, PMID 32677986.

Giri M, Zhang M, Lu YY. Genes associated with Alzheimer’s disease: an overview and current status. Clin Interv Aging. 2016;11:665-81. doi: 10.2147/CIA.S105769, PMID 27274215.

Castellani RJ, Zhu X, Lee HG, Smith MA, Perry G. Molecular pathogenesis of Alzheimer’s disease: reductionist versus expansionist approaches. Int J Mol Sci. 2009 Mar;10(3):1386-406. doi: 10.3390/ijms10031386, PMID 19399255.

Smith MA, Rottkamp CA, Nunomura A, Raina AK, Perry G. Oxidative stress in Alzheimer’s disease. Biochim Biophys Acta. 2000 Jul 26;1502(1):139-44. doi: 10.1016/s0925-4439(00)00040-5, PMID 10899439.

Singh RP, Sharad S, Kapur S. Free radicals and oxidative stress in neurodegenerative diseases: relevance of dietary antioxidants. J Indian Acad Clin Med. 2004 Jul;5:218-25.

Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, Squadrito F, Altavilla D, Bitto A. Oxidative stress: harms and benefits for human health. Oxid Med Cell Longev. 2017 Oct;2017:8416763. doi: 10.1155/2017/8416763, PMID 28819546.

Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem. 2015 Jan 1;30(1):11-26. doi: 10.1007/s12291-014-0446-0, PMID 25646037.

Khan F, Kumar Garg V, Kumar Singh A, Tinku T, Khan F, Garg VK, Singh AK. Role of free radicals and certain antioxidants in the management of huntington’s disease: a review. J Anal Pharm Res. 2018;7(4):386-92. DOI: 10.15406/japlr.2018.07.00256.

Al-Dalaen SM. Oxidative stress versus antioxidants. Am J Biosci Bioeng. 2014 Dec 3;2(5):60. doi: 10.11648/j.bio.20140205.11.

Breitenbach M, Eckl P. Introduction to oxidative stress in biomedical and biological research. Biomolecules. 2015;5(2):1169-77. doi: 10.3390/biom5021169, PMID 26117854.

Halliwell BE. Free radicals, reactive oxygen species and human disease: a critical evaluation with special reference to atherosclerosis. Br J Exp Pathol. 1989 Dec; 70(6):737–57. PMID: PMID: 2557883.

Nash KM, Rockenbauer A, Villamena FA. Reactive nitrogen species reactivities with nitrones: theoretical and experimental studies. Chem Res Toxicol. 2012 Aug 20;25(8):1581-97. doi: 10.1021/tx200526y, PMID 22775566.

Ozcan A, Ogun M. Biochemistry of reactive oxygen and nitrogen species. In: Basic principles and clinical significance of oxidative stress. Chapter: 3; 2015. p. 37-58.

Martinez MC, Andriantsitohaina R. Reactive nitrogen species: molecular mechanisms and potential significance in health and disease. Antioxid Redox Signal. 2009 Mar 1;11(3):669-702. doi: 10.1089/ars.2007.1993, PMID 19014277.

Noori S. An overview of oxidative stress and antioxidant defensive system. J Clin Cell Immunol. 2012;1(8):1-9. doi: 10.4172/scientificreports.413.

Persson T, Popescu BO, Cedazo-Minguez A. Oxidative stress in Alzheimer’s disease: why did antioxidant therapy fail? Oxid Med Cell Longev. 2014 Oct;2014:427318. doi: 10.1155/2014/427318, PMID 24669288.

Huang WJ, Zhang XI, Chen WW. Role of oxidative stress in Alzheimer’s disease. Biomed Rep. 2016 May 1;4(5):519-22. doi: 10.3892/br.2016.630, PMID 27123241.

Chakrabarti S, Munshi S, Banerjee K, Thakurta IG, Sinha M, Bagh MB. Mitochondrial dysfunction during brain aging: role of oxidative stress and modulation by antioxidant supplementation. Aging Dis. 2011 Jun;2(3):242-56. PMID 22396876.

Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: impact on human health. Pharmacogn Rev. 2010 Jul;4(8):118-26. doi: 10.4103/0973-7847.70902, PMID 22228951.

Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J. 2016 Dec;15(1):71. doi: 10.1186/s12937-016-0186-5, PMID 27456681.

Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci. 2008 Jun;4(2):89-96. PMID 23675073.

Markesbery WR. The role of oxidative stress in Alzheimer disease. Arch Neurol. 1999 Dec 1;56(12):1449-52. doi: 10.1001/archneur.56.12.1449, PMID 10593298.

O’brien RJ, Wong PC. Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci. 2011 Jul 21;34:185-204. doi: 10.1146/annurev-neuro-061010-113613, PMID 21456963.

Galvão Jr F, Grokoski KC, da Silva BB, Lamers ML, Siqueira IR. The amyloid precursor protein (APP) processing as a biological link between Alzheimer’s disease and cancer. Ageing Res Rev. 2019 Jan 1;49:83-91. doi: 10.1016/j.arr.2018.11.007, PMID 30500566.

Zhang YW, Thompson R, Zhang H, Xu H. APP processing in Alzheimer’s disease. Mol Brain. 2011 Dec;4:3. doi: 10.1186/1756-6606-4-3, PMID 21214928.

Kametani F, Hasegawa M. Reconsideration of amyloid hypothesis and tau hypothesis in Alzheimer’s disease. Front Neurosci. 2018 Jan 30;12:25. doi: 10.3389/fnins.2018.00025, PMID 29440986.

de Paula VJR, Guimaraes FM, Diniz BS, Forlenza OV. Neurobiological pathways to Alzheimer’s disease: amyloid-beta, Tau protein or both? Dement Neuropsychol. 2009 Jul;3(3):188-94. doi: 10.1590/S1980-57642009DN30300003, PMID 29213627.

Cheignon C, Tomas M, Bonnefont Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid-beta peptide in Alzheimer’s disease. Redox Biol. 2018;14:450-64. doi: 10.1016/j.redox.2017.10.014, PMID 29080524.

Butterfield DA, Swomley AM, Sultana R. Amyloid β-peptide (1-42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression. Antioxid Redox Signal. 2013 Sep 10;19(8):823-35. doi: 10.1089/ars.2012.5027, PMID 23249141.

Seeman P, Seeman N. Alzheimer’s disease: β‐amyloid plaque formation in human brain. Synapse. 2011 Dec;65(12):1289-97. doi: 10.1002/syn.20957, PMID 21633975.

Li NM, Liu KF, Qiu YJ, Zhang HH, Nakanishi H, Qing H. Mutations of beta-amyloid precursor protein alter the consequence of Alzheimer’s disease pathogenesis. Neural Regen Res. 2019 Apr;14(4):658-65. doi: 10.4103/1673-5374.247469, PMID 30632506.

Tcw J, Goate AM. Genetics of β-amyloid precursor protein in Alzheimer’s disease. Cold Spring Harb Perspect Med. 2017 Jun 1;7(6):a024539. doi: 10.1101/cshperspect.a024539, PMID 28003277.

Sun X, Chen WD, Wang YD. β-amyloid: the key peptide in the pathogenesis of Alzheimer’s disease. Front Pharmacol. 2015 Sep 30;6:221. doi: 10.3389/fphar.2015.00221, PMID 26483691.

Stakos DA, Stamatelopoulos K, Bampatsias D, Sachse M, Zormpas E, Vlachogiannis NI, Tual-Chalot S, Stellos K. The Alzheimer’s disease amyloid-beta hypothesis in cardiovascular aging and disease: JACC focus seminar. J Am Coll Cardiol. 2020 Mar 3;75(8):952-67. doi: 10.1016/j.jacc.2019.12.033, PMID 32130931.

Wojsiat J, Zoltowska KM, Laskowska-Kaszub K, Wojda U. Oxidant/antioxidant imbalance in Alzheimer’s disease: therapeutic and diagnostic prospects. Oxid Med Cell Longevity. 2018 Oct; 2018:6435861. doi: 10.1155/2018/6435861, PMID 29636850.

Ridge PG, Ebbert MT, Kauwe JS. Genetics of Alzheimer’s disease. BioMed Res Int. 2013 Jan 1;2013:254954. doi: 10.1155/2013/254954, PMID 23984328.

Zuo L, Hemmelgarn BT, Chuang CC, Best TM. The role of oxidative stress-induced epigenetic alterations in amyloid-β production in Alzheimer’s disease. Oxid Med Cell Longevity. 2015 Oct 11;2015:604658. doi: 10.1155/2015/604658, PMID 26543520.

Liu Z, Li T, Li P, Wei N, Zhao Z, Liang H, Ji X, Chen W, Xue M, Wei J. The ambiguous relationship of oxidative stress, tau hyperphosphorylation, and autophagy dysfunction in Alzheimer’s disease. Oxid Med Cell Longevity. 2015 Oct; 2015:352723. doi: 10.1155/2015/352723, PMID 26171115.

Kang SW, Kim SJ, Kim MS. Oxidative stress with tau hyperphosphorylation in memory impaired 1, 2-diacetylbenzene-treated mice. Toxicol Lett 2017 Sep 5;279:53-9. doi: 10.1016/j.toxlet.2017.07.892, PMID 28734998.

Mondragon Rodriguez S, Perry G, Zhu X, Moreira PI, Acevedo-Aquino MC, Williams S. Phosphorylation of Tau protein as the link between oxidative stress, mitochondrial dysfunction, and connectivity failure: implications for Alzheimer’s disease. Oxid Med Cell Longevity. 2013 Oct; 2013:940603. doi: 10.1155/2013/940603, PMID 23936615.

Ibanez Salazar A, Banuelos Hernandez B, Rodriguez Leyva I, Chi-Ahumada E, Monreal Escalante E, Jimenez Capdeville ME, Rosales Mendoza S. Oxidative stress modifies the levels and phosphorylation state of Tau protein in human fibroblasts. Frontiers Neurosci. 2017 Sep 7;11:495. doi: 10.3389/fnins.2017.00495, PMID 28936161.

Haque MM, Murale DP, Kim YK, Lee JS. Crosstalk between oxidative stress and tauopathy. Int J Mol Sci. 2019 Jan;20(8):19592019. doi: 10.3390/ijms20081959, PMID 31013607.

Sadigh Eteghad S, Sabermarouf B, Majdi A, Talebi M, Farhoudi M, Mahmoudi J. Amyloid-beta: a crucial factor in Alzheimer'’s disease. Med Principles Practice. 2015;24(1):1-01-10. doi: 10.1159/000369101, PMID 25471398.

Hurtado DE, Molina-Porcel L, Iba M, Aboagye AK, Paul SM, Trojanowski JQ, Lee VM. Aβ accelerates the spatiotemporal progression of tau pathology and augments tau amyloidosis in an Alzheimer mouse model. Am J Pathol. 2010 Oct 1;177(4):1977-88. doi: 10.2353/ajpath.2010.100346, PMID 20802182.

Mattsson-Carlgren N, Andersson E, Janelidze S, Ossenkoppele R, Insel P, Strandberg O, Zetterberg H, Rosen HJ, Rabinovici G, Chai X, Blennow K, Dage JL, Stomrud E, Smith R, Palmqvist S, Hansson O. Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer’s disease. Sci Adv. 2020 Apr 1;6(16):eaaz2387. doi: 10.1126/sciadv.aaz2387, PMID 32426454.

Perry G, Moreira PI, Santos MS, Oliveira CR, Shenk JC, Nunomura A, Smith MA, Zhu X. Alzheimer disease and the role of free radicals in the pathogenesis of the disease. CNS Neurol Disorders Drug Targets 2008 Feb 1;7:3-10.

Maurer SV, Williams CL. The cholinergic system modulates memory and hippocampal plasticity via its interactions with non-neuronal cells. Frontiers Immunol. 2017 Nov 8;8:1489. doi: 10.3389/fimmu.2017.01489, PMID 29167670.

Halder N, Lal G. Cholinergic system and its therapeutic importance in inflammation and autoimmunity. Frontiers Immunol. 2021;12:660342. doi: 10.3389/fimmu.2021.660342, PMID 33936095.

Beckmann J, Lips KS. The non-neuronal cholinergic system in health and disease. Pharmacology. 2013;92(5-6):286-302. doi: 10.1159/000355835, PMID 24296914.

Chiroma SM, Taib CNM, Moklas MAM, Baharuldin MTH, Amom Z, Jagadeesan S. The use of nootropics in Alzheimer’s disease: is there light at the end of the tunnel? Biomed Res Ther. 2019 Jan 4;6(1):2937-44. doi: 10.15419/bmrat.v6i1.513.

Colovic MB, Krstic DZ, Lazarevic-Pasti TD, Bondziczic AM, Vasic VM. Acetyl cholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol. 2013 May 1;11(3):315-35. doi: 10.2174/1570159X11311030006, PMID 24179466.

Garcia Ayllon MS, Small DH, Avila J, Saez Valero J. Revisiting the role of acetylcholinesterase in Alzheimer’s disease: cross-talk with P-tau and β-amyloid. Frontiers Mol Neurosci 2011 Sep 13;4:22. doi: 10.3389/fnmol.2011.00022, PMID 21949503.

Hampel H, Mesulam MM, Cuello AC, Khachaturian AS, Vergallo A, Farlow MR, Snyder PJ, Giacobini E, Khachaturian ZS. Revisiting the cholinergic hypothesis in Alzheimer’s disease: emerging evidence from translational and clinical research. J Prevention Alzheimer's Disease. 2019 Jan; 6(1):2-15. doi: 10.14283/jpad.2018.43, PMID 30569080.

Mattson MP, Pedersen WA. Effects of amyloid precursor protein derivatives and oxidative stress on basal forebrain cholinergic systems in Alzheimer’s disease. Int J Dev Neurosci. 1998 Nov 1;16(7-8):737-53. doi: 10.1016/s0736-5748(98)00082-3, PMID 10198821.

McGirr S, Venegas C, Swaminathan A. Alzheimers ddisease: a bbrief rreview. J Exp Neurol. 2020 Jul 29;1.

Black SA, Rylett RJ. Impact of oxidative-nitrosative stress on cholinergic presynaptic function. Alzheimer’s Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets. InTtech. 2011 Sep 12:p345-68.



How to Cite

G., S., A. RAJ, S. TABASSUM, and D. Z. CHHAKCHHUAK. “OXIDATIVE STRESS IN ALZHEIMER’S DISEASE–EVALUATING THE AMYLOID BETA HYPOTHESIS”. International Journal of Current Pharmaceutical Research, vol. 13, no. 5, Sept. 2021, pp. 32-38, doi:10.22159/ijcpr.2021v13i5.1906.



Review Article(s)