Authors : Riddhi Rane; Bhagya V Rao; Joshnavi Tadimari

Volume/Issue : Volume 10 - 2025, Issue 4 - April

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DOI : https://doi.org/10.38124/ijisrt/25apr828

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Abstract : Background Alzheimer’s disease (AD), the most common neurodegenerative disorder, is driven by amyloid-beta (Aβ) plaques, neurofibrillary tangles (NFTs), neuroinflammation, and oxidative stress. Rodent models are critical for studying its multifactorial etiology, combining genetic, environmental, and epigenetic factors. This review evaluates rodent AD models, including chemical induction (e.g., aluminum, scopolamine) and transgenic systems (e.g., 5xFAD, APP/PS1). Chemical models mimic sporadic AD triggers, while transgenics replicate genetic mutations. Combinatorial approaches (e.g., toxin- exposed transgenics) address limitations. Biomarkers such as Aβ/tau ratios, neuroinflammatory cytokines (TNF-α, IL-1β), and oxidative stress markers (MDA, SOD) validate pathology, measured via ELISA, PET imaging, and omics technologies.

Keywords : Alzheimer Disease; Biomarkers, Animal Models, Pathophysiology, Neuroinflammation

References :

1. Zhang H, Tahami Monfared AA, Zhang Q, Honig LS. Incidence and prevalence of Alzheimer's disease in medicare beneficiaries. Neurol Ther. 2025;14(1):319-333. doi: 10.1007/s40120-024-00695-6.
2. 2024 Alzheimer's disease facts and figures. Alzheimers Dement. 2024;20(5):3708-3821. doi: 10.1002/alz.13809.
3. Sajad M, Ali R, Kumar R, khan NJ, Wahab S, Alshehri SA, et al. β-Sitosterol ameliorates the cognitive deficits and neuropathological hallmarks in an Alzheimer’s disease model. Arab J Chem2025; 18 (1). 106072.https://doi.org/10.1016/j.arabjc.2024.106072.
4. Morgese MG, Bove M, Di Cesare Mannelli L, Schiavone S, Colia AL, Dimonte S, et al. Precision medicine in Alzheimer’sdisease: Investigating comorbid common biological substrates in the rat model of amyloid beta-induced toxicity. Front Pharmacol 2022; 12:799561.doi: 10.3389/fphar.2021.799561.
5. Han G, Xuewu G, Meng Z, Yuejing W, Yuchun W, Keshuang Z, et al. Therapeutic effect of dihydroartemisinin on Alzheimer’s disease model mice with senile macular degeneration. Eur J Med Res 2025; 30 (1):81. https://doi.org/10.1186/s40001-025-02315-x.
6. Sun X ying, Li L jie, Dong QX, Zhu J, Huang Y ru, Hou S jie, et al. Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer’s disease. J Neuroinflammation 2021; 18(1):131. doi: 10.1186/s12974-021-02182-3.
7. Lakshmi BVS, Sudhakar M, Prakash KS. Protective effect of selenium against aluminum chloride-induced Alzheimer’s disease: Behavioral and biochemical alterations in rats. Biol Trace Elem Res 2015; 165(1):67–74. https://doi.org/10.1007/s12011-015-0229-3.
8. Stoiljkovic M, Kelley C, Horvath TL, Hajós M. Neurophysiological signals as predictive translational biomarkers for Alzheimer’s disease treatment: Effects of donepezil on neuronal network oscillations in TgF344-AD rats. Alzheimers Res Ther 2018;10(1):105. doi: 10.1186/s13195-018-0433-4.
9. Chen X, Zhang M, Ahmed M, Surapaneni KM, Veeraraghavan VP, Arulselvan P. Neuroprotective effects of ononin against the aluminium chloride-induced Alzheimer’s disease in rats. Saudi J Biol Sci. 2021;28(8):4232-4239. doi: 10.1016/j.sjbs.2021.06.031.
10. Granzotto A, Vissel B, Sensi SL. Lost in translation: Inconvenient truths on the utility of mouse models in Alzheimer’s disease research. Elife 2024; 13:e90633.doi: 10.7554/eLife.90633.
11. Gurdon B, Kaczorowksi C. Pursuit of precision medicine: Systems biology approaches in Alzheimer’s disease mouse models. Neurobiol Dis 2021; 161:105558.doi: 10.1016/j.nbd.2021.105558.
12. Firdaus Z, Kumar D, Singh SK, Singh TD. Centella asiaticaalleviates AlCl3-induced cognitive impairment, oxidative stress, and neurodegeneration by modulating cholinergic activity and oxidative burden in rat brain. Biol Trace Elem Res. 2022;200(12):5115-5126. doi: 10.1007/s12011-021-03083-5.
13. Justin Thenmozhi A, Dhivyabharathi M, William Raja TR, Manivasagam T, Essa MM. Tannoid principles of Emblica officinalis renovate cognitive deficits and attenuate amyloid pathologies against aluminum chloride induced rat model of Alzheimer’s disease. Nutr Neurosci. 2016;19(6):269-278. doi: 10.1179/1476830515Y.0000000016.
14. El-Sawi SA, Ezzat SM, Aly HF, Merghany RM, Meselhy MR. Neuroprotective effect of Salvia splendens extract and its constituents against AlCl3-induced Alzheimer’s disease in rats. AdvTradit Med 2020; 20:381–393. https://doi.org/10.1007/s13596-019-00421-w.
15. Kazmi I, Afzal M, Imam F, Alzarea SI, Patil S, Mhaiskar A, et al. Barbaloin’s chemical intervention in aluminum chloride induced cognitive deficits and changes in rats through modulation of oxidative stress, cytokines, and BDNF expression. ACS Omega. 2024;9(6):6976-6985. doi: 10.1021/acsomega.3c08791.
16. Cao Z, Wang F, Xiu C, Zhang J, Li Y. Hypericum perforatum extract attenuates behavioral, biochemical, and neurochemical abnormalities in Aluminum chloride-induced Alzheimer’s disease rats. Biomed Pharmacother2017; 91:931–937. https://doi.org/10.1016/j.biopha.2017.05.022.
17. Zhao Y, Dang M, Zhang W, Lei Y, Ramesh T, Priya Veeraraghavan V, et al. Neuroprotective effects of Syringic acid against aluminium chloride induced oxidative stress mediated neuroinflammation in rat model of Alzheimer’s disease. J Funct Foods 2020; 71: 104009.  https://doi.org/10.1016/j.jff.2020.104009.
18. Promyo K, Iqbal F, Chaidee N, Chetsawang B. Aluminum chloride-induced amyloid β accumulation and endoplasmic reticulum stress in rat brain are averted by melatonin. Food Chem Toxicol. 2020;146:111829. doi: 10.1016/j.fct.2020.111829.
19. Chiroma SM, Mohd Moklas MA, Mat Taib CN, Baharuldin MTH, Amon Z. D-galactose and aluminium chloride induced rat model with cognitive impairments. Biomed Pharmacother. 2018;103:1602-1608. doi: 10.1016/j.biopha.2018.04.152.
20. Dan L, Hao Y, Li J, Wang T, Zhao W, Wang H, et al. Neuroprotective effects and possible mechanisms of berberine in animal models of Alzheimer's disease: a systematic review and meta-analysis. Front Pharmacol. 2024; 14:1287750. doi: 10.3389/fphar.2023.1287750.
21. Safar MM, Arab HH, Rizk SM, El-Maraghy SA. Bone marrow-derived endothelial progenitor cells protect against scopolamine-induced Alzheimer-like pathological aberrations. Mol Neurobiol. 2016;53(3):1403-1418. doi: 10.1007/s12035-014-9051-8.
22. Bhuvanendran S, Kumari Y, Othman I, Shaikh MF. Amelioration ofcognitive deficit by embelin in a scopolamine-induced Alzheimer’s disease-like condition in a rat model. Front Pharmacol. 2018;9:665. doi: 10.3389/fphar.2018.00665.
23. Yadang FSA, Nguezeye Y, Kom CW, Betote PHD, Mamat A, Tchokouaha LRY, et al. Scopolamine-induced memory impairment in mice: Neuroprotective effects of Carissa edulis (Forssk.) Valh (Apocynaceae) aqueous extract.  Int J Alzheimers Dis. 2020;2020:6372059. doi: 10.1155/2020/6372059.
24. Aykac A, Ozbeyli D, Uncu M, Ertaş B, Kılınc O, Şen A, et al. Evaluation of the protective effect of Myrtus communis in scopolamine-induced Alzheimer model through cholinergic receptors. Gene. 2019;689:194-201. doi: 10.1016/j.gene.2018.12.007.
25. Rajashri K, Mudhol S, Serva Peddha M, Borse BB. Neuroprotective effect of spice oleoresins on memory and cognitive impairment associated with scopolamine-induced Alzheimer’s disease in rats. ACS Omega 2020; 5 (48):30898–30905. https://doi.org/10.1021/acsomega.0c03689.
26. Safarzadeh E, Ataei S, Akbari M, Abolhasani R, Baziar M, Asghari-Azar V, et al. Quercetin ameliorates cognitive deficit, expression of amyloid precursor gene, and pro-inflammatory cytokines in an experimental models of Alzheimer’s disease in Wistar rats. Exp Gerontol 2024; 193: 112466. https://doi.org/10.1016/j.exger.2024.112466.
27. Decandia D, Gelfo F, Landolfo E, Balsamo F, Petrosini L, Cutuli D. Dietary protection against cognitive impairment, neuroinflammation and oxidative stress in Alzheimer’s disease animal models of lipopolysaccharide-induced inflammation. Int J Mol Sci. 2023;24(6):5921. doi: 10.3390/ijms24065921.
28. Choe K, Park JS, Park HY, Tahir M, Park TJ, Kim MO. Lupeol protect against LPS-induced neuroinflammation and amyloid beta in adult mouse hippocampus. Front Nutr. 2024;11:1414696. doi: 10.3389/fnut.2024.1414696.
29. Hayashi K, Hasegawa Y, Takemoto Y, Cao C, Takeya H, Komohara Y, et al. Continuous intracerebroventricular injection of Porphyromonas gingivalis lipopolysaccharide induces systemic organ dysfunction in a mouse model of Alzheimer’s disease. Exp Gerontol. 2019;120:1-5. doi: 10.1016/j.exger.2019.02.007.
30. Go J, Chang DH, Ryu YK, Park HY, Lee IB, Noh JR, et al. Human gut microbiota Agathobaculum butyriciproducens improves cognitive impairment in LPS-induced and APP/PS1 mouse models of Alzheimer’s disease. Nutr Res. 2021;86:96-108. doi: 10.1016/j.nutres.2020.12.010.
31. Abd Elmaaboud MA, Estfanous RS, Atef A, Kabel AM, Alnemari KA, Naguib TM, et al. Dapagliflozin/hesperidin combination mitigates lipopolysaccharide-induced Alzheimer's disease in rats. Pharmaceuticals (Basel). 2023;16(10):1370. doi: 10.3390/ph16101370.
32. Sun J, Zhang S, Zhang X, Zhang X, Dong H, Qian Y. IL-17A is implicated in lipopolysaccharide-induced neuroinflammation and cognitive impairment in aged rats via microglial activation. J Neuroinflammation. 2015;12:165. doi: 10.1186/s12974-015-0394-5.
33. Nabil-Adam A, Ashour ML, Shreadah MA. Modulation of MAPK/NF-κB pathway and NLRP3 inflammasome by secondary metabolites from red algae: A mechanistic study. ACS Omega. 2023;8(41):37971-37990. doi: 10.1021/acsomega.3c03480.
34. Kim YE, Hwang CJ, Lee HP, Kim CS, Son DJ, Ham YW, et al. Inhibitory effect of punicalagin on lipopolysaccharide-induced neuroinflammation, oxidative stress and memory impairment via inhibition of nuclear factor-kappaB. Neuropharmacology. 2017;117:21-32. doi: 10.1016/j.neuropharm.2017.01.025.
35. Abbas HA, Salama AM, El-Toumy SA, Salama AAA, Tadros SH, Gedaily RAE. Novel neuroprotective potential of Bunchosia armeniaca (Cav.) DC against lipopolysaccharide induced Alzheimer’s disease in mice. Plants (Basel). 2022;11(14):1792. doi: 10.3390/plants11141792.
36. Guo Z, Chen Y, Mao YF, Zheng T, Jiang Y, Yan Y, et al. Long-term treatment with intranasal insulin ameliorates cognitive impairment, tau hyperphosphorylation, and microglial activation in a streptozotocin-induced Alzheimer’s rat model. Sci Rep 2017; 7: 45971. https://doi.org/10.1038/srep45971.
37. Wei J, Yang F, Gong C, Shi X, Wang G. Protective effect of daidzein against streptozotocin-induced Alzheimer's disease via improving cognitive dysfunction and oxidative stress in rat model. J Biochem Mol Toxicol. 2019; 33(6): e22319. doi: 10.1002/jbt.22319.
38. Sirwi A, Sayed NSE, Abdallah HM, Ibrahim SRM, Mohamed GA, El-Halawany AM, et al. Umuhengerin neuroprotective effects in streptozotocin-induced Alzheimer’s disease mouse model via targeting nrf2 and Nrf2 and NF-Kβ signaling cascades.  Antioxidants (Basel). 2021; 10(12): 2011. doi: 10.3390/antiox10122011.
39. Ravelli KG, Rosário B dos A, Camarini R, Hernandes MS, Britto LR. Intracerebroventricular streptozotocin as a model of Alzheimer’s disease: Neurochemical and behavioral characterization in mice. Neurotox Res 2017; 31(3): 327-333. https://doi.org/10.1007/s12640-016-9684-7.
40. Knezovic A, Osmanovic-Barilar J, Curlin M, Hof PR, Simic G, Riederer P, et al. Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer’s disease. J Neural Transm 2015; 122(4): 577-592. doi: 10.1007/s00702-015-1394-4.
41. Sarathlal KC, Kakoty V, Marathe S, Chitkara D, Taliyan R. Exploring the neuroprotective potential of rosiglitazone embedded nanocarrier system on streptozotocin induced mice model of Alzheimer’s disease. Neurotox Res 2021; 39(2): 240-255. doi: 10.1007/s12640-020-00258-1.
42. de Paula Faria D, Estessi de Souza L, Duran FL de S, Buchpiguel CA, Britto LR, Crippa JA de S, et al. Cannabidiol treatment improves glucose metabolism and memory in streptozotocin-induced Alzheimer’s disease rat model: A proof-of-concept study. Int J Mol Sci. 2022; 23(3): 1076. doi: 10.3390/ijms23031076.
43. Sorial ME, El Sayed NSED. Protective effect of valproic acid in streptozotocin-induced sporadic Alzheimer’s disease mouse model: possible involvement of the cholinergic system. Naunyn Schmiedebergs Arch Pharmacol. 2017; 390(6): 581-593. doi: 10.1007/s00210-017-1357-4.
44. Retinasamy T, Shaikh MF, Kumari Y, Abidin SAZ, Othman I. Orthosiphon stamineus standardized extract reverses streptozotocin-induced Alzheimer’s disease-like condition in a rat model. Biomedicines. 2020; 8(5): 104. doi: 10.3390/biomedicines8050104.
45. Hira S, Saleem U, Anwar F, Sohail MF, Raza Z, Ahmad B. β-Carotene: A natural compound improves cognitive impairment and oxidative stress in a mouse model of streptozotocin-induced Alzheimer’s disease. Biomolecules. 2019; 9(9): 441. doi: 10.3390/biom9090441.
46. Joy T, Rao MS, Madhyastha S, Pai K. Effect of N-acetyl cysteine on intracerebroventricular colchicine induced cognitive deficits, beta amyloid pathology, and glial cells. Neurosci J. 2019; 2019: 7547382. doi: 10.1155/2019/7547382.
47. Saini N, Singh D, Sandhir R. Bacopa monnieri prevents colchicine-induced dementia by anti-inflammatory action. Metab Brain Dis. 2019; 34(2): 505-518. doi: 10.1007/s11011-018-0332-1.
48. Ogunro OB, Karigidi ME, Gyebi GA, Turkistani A, Almehmadi AH. Tangeretin offers neuroprotection against colchicine-induced memory impairment in Wistar rats by modulating the antioxidant milieu, inflammatory mediators and oxidative stress in the brain tissue. BMC Complement Med Ther. 2025; 25(1): 40. doi: 10.1186/s12906-025-04769-2.
49. Kumar A, Aggrawal A, Pottabathini R, Singh A. Possible neuroprotective mechanisms of clove oil against icv-colchicine induced cognitive dysfunction. Pharmacol Rep. 2016; 68(4): 764-772. doi: 10.1016/j.pharep.2016.03.005.
50. Jiang X, Kumar M, Zhu Y. Protective effect of hyperforin on β amyloid protein induced apoptosis in PC12 cells and colchicine induced Alzheimer’s disease: An anti-oxidant and anti-inflammatory therapy. J Oleo Sci. 2018; 67(11): 1443-1453. doi: 10.5650/jos.ess18117.
51. Sil S, Ghosh T. Role of cox-2 mediated neuroinflammation on the neurodegeneration and cognitive impairments in colchicine induced rat model of Alzheimer’s disease. J Neuroimmunol. 2016; 291: 115-124. doi: 10.1016/j.jneuroim.2015.12.003.
52. Nazari-Serenjeh M, Baluchnejadmojarad T, Hatami-Morassa M, Fahanik-Babaei J, Mehrabi S, Tashakori-Miyanroudi M, et al. Kolaviron neuroprotective effect against okadaic acid-provoked cognitive impairment. Heliyon 2024; 10(3): e25564. https://doi.org/10.1016/j.heliyon.2024.e25564.
53. Cakir M, Duzova H, Tekin S, Taslıdere E, Kaya GB, Cigremis Y, et al. ACA, an inhibitor phospholipases A2 and transient receptor potential melastatin-2 channels, attenuates okadaic acid induced neurodegeneration in rats. Life Sci. 2017; 176: 10-20. doi: 10.1016/j.lfs.2017.03.022.
54. Dubey R, Sathiyanarayanan L, Sankaran S, Arulmozhi S. Nootropic effect of Indian Royal Jelly against okadaic acid induced rat model of Alzheimer’s disease: Inhibition of neuroinflammation and acetylcholineesterase. J Tradit Complement Med. 2023; 14(3): 300-311. doi: 10.1016/j.jtcme.2023.11.005.
55. Zhao L, Xiao Y, Wang XL, Pei J, Guan ZZ. Original Research: Influence of okadaic acid on hyperphosphorylation of tau and nicotinic acetylcholine receptors in primary neurons. Exp Biol Med (Maywood). 2016; 241(16): 1825-1833. doi: 10.1177/1535370216650759.
56. Sachdeva AK, Chopra K. Naringin mitigate okadaic acid-induced cognitive impairment in an experimental paradigm of Alzheimer’s disease. J Funct Foods 2015; 19: 110-125. https://doi.org/10.1016/j.jff.2015.08.024.
57. Wang Y, Song X, Liu D, Lou Y xia, Luo P, Zhu T, et al. IMM-H004 reduced okadaic acid-induced neurotoxicity by inhibiting Tau pathology in vitro and in vivo. Neurotoxicology. 2019; 75: 221-232. doi: 10.1016/j.neuro.2019.09.012.
58. Zhang SF, Dong YC, Zhang XF, Wu XG, Cheng JJ, Guan LH, et al. Flavonoids from Scutellaria attenuate okadaic acid-induced neuronal damage in rats. Brain Inj. 2015; 29(11): 1376-1382. doi: 10.3109/02699052.2015.1042053.
59. Akinyemi AJ, Adeniyi PA. Effect of essential oils from ginger (Zingiber officinale) and turmeric (Curcuma longa) rhizomes on some inflammatory biomarkers in cadmium induced neurotoxicity in rats. J Toxicol. 2018; 2018: 4109491. doi: 10.1155/2018/4109491.
60. Afifi O, Embaby A. Histological study on the protective role of ascorbic acid on cadmium induced cerebral cortical neurotoxicity in adult male albino rats. J Microsc Ultrastruct. 2016; 4(1): 36-45. doi: 10.1016/j.jmau.2015.10.001.
61. Deng P, Fan T, Gao P, Peng Y, Li M, Li J, et al. SIRT5-mediated desuccinylation of rab7a protects against cadmium-induced Alzheimer’s disease-like pathology by restoring autophagic flux. Adv Sci (Weinh). 2024; 11(30): e2402030. doi: 10.1002/advs.202402030.
62. Amer AS, Ali EHA, Zahra MM, Sabry HA. Mesenchymal stem cell-derived exosomes modulate the COX-IV pathway via inhibition of amyloidogenesis and mitoprotection in sodium azide- Alzheimer model in rats. Sci Afr 2024; 25: e02274. https://doi.org/10.1016/j.sciaf.2024.e02274.
63. O’Leary TP, Brown RE. Visuo-spatial learning and memory impairments in the 5xFAD mouse model of Alzheimer’s disease: Effects of age, sex, albinism, and motor impairments. Genes Brain Behav. 2022; 21(4): e12794. doi: 10.1111/gbb.12794.
64. Ojo OA, Rotimi DE, Ojo AB, Ogunlakin AD, Ajiboye BO. Gallic acid abates cadmium chloride toxicity via alteration of neurotransmitters and modulation of inflammatory markers in Wistar rats. Sci Rep. 2023; 13(1): 1577. doi: 10.1038/s41598-023-28893-6.
65. Karthick C, Nithiyanandan S, Essa MM, Guillemin GJ, Jayachandran SK, Anusuyadevi M. Time-dependent effect of oligomeric amyloid-β (1–42)-induced hippocampal neurodegeneration in rat model of Alzheimer’s disease. Neurol Res. 2019; 41(2): 139-150. doi: 10.1080/01616412.2018.1544745.
66. Batool Z, Agha F, Tabassum S, Batool TS, Siddiqui RA, Haider S. Prevention of cadmium-induced neurotoxicity in rats by essential nutrients present in nuts. Acta Neurobiol Exp (Wars) 2019; 79(2): 169-183. https://doi.org/10.21307/ane-2019-015.
67. Al-Brakati A, Albarakati AJA, Lokman MS, Theyab A, Algahtani M, Menshawi S, et al. Possible role of kaempferol in reversing oxidative damage, inflammation, and apoptosis-mediated cortical injury following cadmium exposure. Neurotox Res. 2021; 39(2): 198-209. doi: 10.1007/s12640-020-00300-2.
68. Adefegha SA, Oboh G, Omojokun OS, Adefegha OM. Alterations of Na+/K+-ATPase, cholinergic and antioxidant enzymes activity by protocatechuic acid in cadmium-induced neurotoxicity and oxidative stress in Wistar rats. Biomed Pharmacother. 2016; 83: 559-568. https://doi.org/10.1016/j.biopha.2016.07.017.
69. Alnahdi HS, Sharaf IA. Possible prophylactic effect of omega-3 fatty acids on cadmium-induced neurotoxicity in rats’ brains. Environ Sci Pollut Res Int. 2019; 26(30): 31254-31262. doi: 10.1007/s11356-019-06259-8.
70. El-kott AF, Bin-Meferij MM, Eleawa SM, Alshehri MM. Kaempferol protects against cadmium chloride-induced memory loss and hippocampal apoptosis by increased intracellular glutathione stores and activation of PTEN/AMPK induced inhibition of Akt/mTOR signaling. Neurochem Res. 2020; 45(2): 295-309. doi: 10.1007/s11064-019-02911-4.
71. Sharma S, Verma S, Kapoor M, Saini A, Nehru B. Alzheimer’s disease like pathology induced six weeks after aggregated amyloid-beta injection in rats: increased oxidative stress and impaired long-term memory with anxiety-like behavior. Neurol Res. 2016; 38(9): 838-850. doi: 10.1080/01616412.2016.1209337.
72. Kheirbakhsh R, Haddadi M, Muhammadnejad A, Abdollahi A, Shahi F, Amanpour-Gharaei B, et al. Long-term behavioral, histological, biochemical and hematological evaluations of amyloid beta-induced Alzheimer’s disease in rat. Acta Neurobiol Exp (Wars). 2018; 78(1): 51-59. https://doi.org/10.21307/ane-2018-004.
73. Xiaoguang W, Jianjun C, Qinying C, Hui Z, Lukun Y, Yazhen S. Establishment of a valuable mimic of alzheimer’s disease in rat animal model by intracerebroventricular injection of composited amyloid beta protein. J Vis Exp. 2018; 137: e56157. doi: 10.3791/56157.
74. Bu XL, Xiang Y, Jin WS, Wang J, Shen LL, Huang ZL, et al. Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies. Mol Psychiatry. 2018; 23(9): 1948-1956. doi: 10.1038/mp.2017.204.
75. He Z, Li X, Wang Z, Cao Y, Han S, Li N, et al. Protective effects of luteolin against amyloid beta-induced oxidative stress and mitochondrial impairments through peroxisome proliferator-activated receptor γ-dependent mechanism in Alzheimer’s disease. Redox Biol. 2023; 66: 102848. doi: 10.1016/j.redox.2023.102848.
76. Baluchnejadmojarad T, Mohamadi-Zarch SM, Roghani M. Safranal, an active ingredient of saffron, attenuates cognitive deficits in amyloid β-induced rat model of Alzheimer’s disease: underlying mechanisms. Metab Brain Dis. 2019; 34(6): 1747-1759. doi: 10.1007/s11011-019-00481-6.
77. Shahidi S, Zargooshnia S, Asl SS, Komaki A, Sarihi A. Influence of N-acetyl cysteine on beta-amyloid-induced Alzheimer’s disease in a rat model: A behavioral and electrophysiological study. Brain Res Bull. 2017; 131: 142-149. doi: 10.1016/j.brainresbull.2017.04.001.
78. Sellers KJ, Elliott C, Jackson J, Ghosh A, Ribe E, Rojo AI, et al. Amyloid β synaptotoxicity is Wnt-PCP dependent and blocked by fasudil. Alzheimers Dement. 2018; 14(3): 306-317. doi: 10.1016/j.jalz.2017.09.008.
79. Beheshti S, Shahmoradi B. Therapeutic effect of Melissa officinalis in an amyloid-β rat model of Alzheimer’s disease. J Herbmed Pharmacol. 2018; 7(3): 193-199. https://doi.org/10.15171/jhp.2018.31.
80. Kim HY, Lee DK, Chung BR, Kim HV, Kim Y. Intracerebroventricular injection of amyloid-β peptides in normal mice to acutely induce Alzheimer-like cognitive deficits. J Vis Exp. 2016; 109: e53308. doi: 10.3791/53308.
81. Hussien HM, Abd-Elmegied A, Ghareeb DA, Hafez HS, Ahmed HEA, El-moneam NA. Neuroprotective effect of berberine against environmental heavy metals-induced neurotoxicity and Alzheimer’s-like disease in rats. Food Chem Toxicol. 2018; 111: 432-444. doi: 10.1016/j.fct.2017.11.025.
82. Huang D, Chen L, Ji Q, Xiang Y, Zhou Q, Chen K, et al. Lead aggravates Alzheimer’s disease pathology via mitochondrial copper accumulation regulated by COX17. Redox Biol. 2024; 69: 102990. doi: 10.1016/j.redox.2023.102990.
83. Korde DS, Humpel C. A combination of heavy metals and intracellular pathway modulators induces Alzheimer disease-like pathologies in organotypic brain slices. Biomolecules. 2024; 14(2): 165. doi: 10.3390/biom14020165.
84. Lin G, Li X, Cheng X, Zhao N, Zheng W. Manganese exposure aggravates β-amyloid pathology by microglial activation. Front Aging Neurosci. 2020; 12: 556008. doi: 10.3389/fnagi.2020.556008.
85. Zhao ZH, Du KJ, Wang T, Wang JY, Cao ZP, Chen XM, et al. Maternal lead exposure impairs offspring learning and memory via decreased GLUT4 membrane translocation. Front Cell Dev Biol. 2021; 9: 648261. doi: 10.3389/fcell.2021.648261.
86. Zhang RY, Zhang L, Zhang L, Wang YL, Li L. Anti-amyloidgenic and neurotrophic effects of tetrahydroxystilbene glucoside on a chronic mitochondrial dysfunction rat model induced by sodium azide. J Nat Med. 2018; 72(3): 596-606. doi: 10.1007/s11418-018-1177-y.
87. Zhang Y, Huang N, Lu H, Huang J, Jin H, Shi J, et al. Icariin protects against sodium azide-induced neurotoxicity by activating the PI3K/Akt/GSK-3β signaling pathway. PeerJ. 2020; 8: e8955. doi: 10.7717/peerj.8955.
88. Olajide OJ, Akinola BO, Ajao SM, Enaibe BU. Sodium azide-induced degenerative changes in the dorsolateral prefrontal cortex of rats: attenuating mechanisms of kolaviron. Eur J Anat. 2016; 20 (1): 47-64. doi:10.1007/s11011-017-0012-6.
89. Olajide OJ, Asogwa NT, Moses BO, Oyegbola CB. Multidirectional inhibition of cortico-hippocampal neurodegeneration by kolaviron treatment in rats. Metab Brain Dis. 2017; 32(4): 1147-1161. doi: 10.1007/s11011-017-0012-6.
90. Krivinko JM, Koppel J, Savonenko A, Sweet RA. Animal models of psychosis in Alzheimer disease. Am J Geriatr Psychiatry. 2020; 28(1): 1-19. doi: 10.1016/j.jagp.2019.05.009.
91. Smit T, Deshayes NAC, Borchelt DR, Kamphuis W, Middeldorp J, Hol EM. Reactive astrocytes as treatment targets in Alzheimer’s disease—Systematic review of studies using the APPswePS1dE9 mouse model. Glia. 2021; 69(8): 1852-1881. doi: 10.1002/glia.23981.
92. Papazoglou A, Henseler C, Weickhardt S, Teipelke J, Papazoglou P, Daubner J, et al. Sex- and region-specific cortical and hippocampal whole genome transcriptome profiles from control and APP/PS1 Alzheimer’s disease mice. PLoS One. 2024; 19(2): e0296959. doi: 10.1371/journal.pone.0296959.
93. Olajide OJ, Enaibe BU, Bankole OO, Akinola OB, Laoye BJ, Ogundele OM. Kolaviron was protective against sodium azide (NaN3) induced oxidative stress in the prefrontal cortex. Metab Brain Dis. 2016; 31(1): 25-35. doi: 10.1007/s11011-015-9674-0.
94. Futácsi A, Rusznák K, Szarka G, Völgyi B, Wiborg O, Czéh B. Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s disease. Front Aging Neurosci. 2025; 17: 1542229. doi: 10.3389/fnagi.2025.1542229.
95. Martens N, Schepers M, Zhan N, Leijten F, Voortman G, Tiane A, et al. 24(S)-saringosterol prevents cognitive decline in a mouse model for Alzheimer’s disease. Mar Drugs. 2021; 19(4): 190. doi: 10.3390/md19040190.
96. Zhai T, Zhang W, Ma C, Ma Y, Paulus YM, Su EJ, et al. Photoacoustic and fluorescence dual-modality imaging of cerebral biomarkers in Alzheimer’s disease rodent model. Biomed Opt. 2024; 29(12): 126002. doi: 10.1117/1.JBO.29.12.126002.
97. Mohammed HE, Nelson JC, Marshall SA. Ethanol exacerbates the Alzheimer’s disease pathology in the 5xFAD mouse model. Neuroglia 2024; 5(3): 289-305. doi: 10.3390/neuroglia5030020.
98. Day SM, Gironda SC, Clarke CW, Snipes JA, Nicol NI, Kamran H, et al. Ethanol exposure alters Alzheimer’s-related pathology, behavior, and metabolism in APP/PS1 mice. Neurobiol Dis. 2023; 177: 105967. doi: 10.1016/j.nbd.2022.105967.
99. Koch G, Casula EP, Bonnì S, Borghi I, Assogna M, Minei M, et al. Precuneus magnetic stimulation for Alzheimer’s disease: a randomized, sham-controlled trial. Brain. 2022; 145(11): 3776-3786. doi: 10.1093/brain/awac285.
100. Majlessi N, Choopani S, Kamalinejad M, Azizi Z. Amelioration of amyloid β-induced cognitive deficits by Zataria multiflora Boiss. essential oil in a rat model of Alzheimer's disease. CNS Neurosci Ther. 2012; 18(4): 295-301. doi: 10.1111/j.1755-5949.2011.00237.x.
101. Wang H, Li Q, Sun S, Chen S. Neuroprotective effects of Salidroside in a mouse model of Alzheimer's disease. Cell Mol Neurobiol. 2020; 40(7): 1133-1142. doi: 10.1007/s10571-020-00801-w.
102. Sun X ying, Yu X lin, Zhu J, Li L jie, Zhang L, Huang Y ru, et al. Fc effector of anti-Aβ antibody induces synapse loss and cognitive deficits in Alzheimer’s disease-like mouse model. Signal Transduct Target Ther. 2023; 8(1): 30. doi: 10.1038/s41392-022-01273-8.
103. Hu Y, Wu L, Jiang L, Liang N, Zhu X, He Q, et al. Notoginsenoside R2 reduces Aβ25-35-induced neuronal apoptosis and inflammation via miR-27a/SOX8/β-catenin axis. Hum Exp Toxicol. 2021; 40(12_suppl): S347-S358. doi: 10.1177/09603271211041996.
104. El-Banna AH, Abo El-Ela FI, Abdel-Wahab A, Gamal A, Abdel-Razik ARH, El-Banna HA, et al. Therapeutic efficacy of amygdaline and amygdaline-loaded niosomes in a rat model of Alzheimer’s disease via oxidative stress, brain neurotransmitters, and apoptotic pathway. Beni-Suef Univ J Basic Appl Sci. 2024; 13: 117. https://doi.org/10.1186/s43088-024-00573-y.
105. Chou CH, Yang CR. Neuroprotective studies of evodiamine in an okadaic acid-induced neurotoxicity. Int J Mol Sci. 2021; 22(10): 5347. doi: 10.3390/ijms22105347.
106. Sil S, Ghosh T, Gupta P, Ghosh R, Kabir SN, Roy A. Dual role of vitamin c on the neuroinflammation mediated neurodegeneration and memory impairments in colchicine induced rat model of Alzheimer disease. J Mol Neurosci. 2016; 60(4): 421-435. doi: 10.1007/s12031-016-0817-5.
107. Ji ZH, Xu ZQ, Zhao H, Yu XY. Neuroprotective effect and mechanism of daucosterol palmitate in ameliorating learning and memory impairment in a rat model of Alzheimer's disease. Steroids. 2017; 119: 31-35. doi: 10.1016/j.steroids.2017.01.003.
108. Ma C, Zhang L, Wang L, Huang Q, Deng Q, Huang F, et al. Ameliorative effect of walnut oil against cognitive impairment in alzheimers type dementia in rodent. Oil Crop Science 2024; 9(4): 234-239. https://doi.org/10.1016/j.ocsci.2024.09.003.
109. Makhaeva GF, Kovaleva NV, Rudakova EV, Boltneva NP, Grishchenko MV, Lushchekina SV, et al. Conjugates of tacrine and salicylic acid derivatives as new promising multitarget agents for Alzheimer's disease. Int J Mol Sci. 2023; 24(3): 2285. doi: 10.3390/ijms24032285.
110. Cui J, Meng YH, Wang ZW, Wang J, Shi DF, Liu D. Ganoderic acids A and B reduce okadaic acid-induced neurotoxicity in PC12 cells by inhibiting tau hyperphosphorylation. Biomed Environ Sci. 2023; 36(1): 103-108. doi: 10.3967/bes2023.011.
111. Ceyzériat K, Gloria Y, Tsartsalis S, Fossey C, Cailly T, Fabis F, et al. Alterations in dopamine system and in its connectivity with serotonin in a rat model of Alzheimer’s disease. Brain Commun. 2021; 3(2): fcab029. doi: 10.1093/braincomms/fcab029.
112. Dubey VK, Ansari F, Vohora D, Khanam R. Possible involvement of corticosterone and serotonin in antidepressant and antianxiety effects of chromium picolinate in chronic unpredictable mild stress induced depression and anxiety in rats. J Trace Elem Med Biol. 2015; 29: 222-226. doi: 10.1016/j.jtemb.2014.06.014.
113. Ramadan WS, Alkarim S. Ellagic acid modulates the amyloid precursor protein gene via superoxide dismutase regulation in the entorhinal cortex in an experimental alzheimer’s model. Cells. 2021; 10(12): 3511. doi: 10.3390/cells10123511.
114. Del Turco D, Paul MH, Schlaudraff J, Hick M, Endres K, Müller UC, et al. Region-specific differences in amyloid precursor protein expression in the mouse hippocampus. Front Mol Neurosci. 2016; 9: 134. doi: 10.3389/fnmol.2016.00134.
115. Bansal A, Kirschner M, Zu L, Cai D, Zhang L. Coconut oil decreases expression of amyloid precursor protein (APP) and secretion of amyloid peptides through inhibition of ADP-ribosylation factor 1 (ARF1). Brain Res. 2019; 1704: 78-84. doi: 10.1016/j.brainres.2018.10.001.
116. Khalaf SS, Hafez MM, Mehanna ET, Mesbah NM, Abo-Elmatty DM. Combined vildagliptin and memantine treatment downregulates expression of amyloid precursor protein, and total and phosphorylated tau in a rat model of combined Alzheimer’s disease and type 2 diabetes.  Naunyn Schmiedebergs Arch Pharmacol. 2019; 392(6): 685-695. doi: 10.1007/s00210-019-01616-3.