Substances administered for the induction of Alzheimer's disease in rats


  • Raquel Barbosa Cordeiro Faculdades Integradas do Vale do Ribeira
  • Fábio Kiss Ticli Faculdades Integradas do Vale do Ribeira
  • Mikael Cavallet Faculdades Integradas do Vale do Ribeira



Alzheimer's disease; induction; chemical substances; rats; beta-amyloid.


Estimates of the progressive expansion of Alzheimer's disease (AD) worldwide indicate the need for constant studies on this pathology, still without cure. Studies have investigated AD in non-human animal models using substances that induced AD. The present study aimed to review the literature on the substances and procedures used in laboratory to reproduce AD in rats. We selected 44 of 111 studies analyzed, keeping only papers that induced AD by chemical substances. The identified substances were aluminum, beta-amyloid, colchicine, d-galactose, scopolamine, streptozocin and homocysteine. It was verified that of the 44 articles, the most used substance was beta-amyloid, the main biomarker of AD. Although different studies have replicated results that simulate the occurrence of AD in rats and the treatments performed with rats in the laboratory appear promising, no cure has yet been found.


Alawdi, S. H., El-Denshary, E. S., Safar, M. M., Eidi, H., David, M. O., & Abdel-Wahhab, M. A. (2016). Neuroprotective Effect of Nanodiamond in Alzheimer’s Disease Rat Model: a Pivotal Role for Modulating NF-Kb and STAT3 Signaling. Molecular Neurobiology, 54(3), 1906-1918.

Alzheimer Disease International (2015). World Alzheimer Report 2015: The Global Impact of Dementia.

American Psychiatric Association (2014). Manual Diagnóstico de Transtornos Mentais. 5ª ed. Porto Alegre: Artmed.

Cazarim M. S., Moriguti, J. C., Ogunjimi, A. T., & Pereira, L. R. L. (2017). Perspectives for treating Alzheimer’s disease: a review on promising pharmacological substances. São Paulo Medical Journal, 134(4), 342-354.

Cevik, B., Solmaz, V., Yigitturk, G., Cavusoğlu, T., Peker, G., & Erbas, O. (2017). Neuroprotective effects of erythropoietin on Alzheimer’s dementia model in rats. Advances in Clinical and Experimental Medicine, 26(1), 23-29.

Chen S-M., Fan C-C., Chiue M-S., Chou C., & Chen J-H. (2013). Hemodynamic and Neuropathological Analysis in Rats with Aluminum Trichloride-Induced Alzheimer’s Disease. PLOS ONE, 8(12), 01-11.

Diling, C., Tianqiao, Y., Jian, Y. Chaoqun, Z., Ou, S. & Yizhen, X. (2017). Docking Studies and Biological Evaluation of a Potential β-Secretase Inhibitor of 3-Hydroxyhericenone F from Hericium erinaceus. Frontiers in Pharmacology, 8(219), 01-17.

Falco, A., Cukierman, D. S., Hauser-Davis R. A., & Rey N. A. (2016). Doença de Alzheimer: hipóteses etiológicas e perspectivas de tratamento. Química Nova, 39(1), 63-80.

Gok, D. K., Ozturk, N., Er, H., Aslan, M., Demir, N., Derin, N., Agar, A., & Yargicoglu, P. (2015). Effects of rosmarinic acid on cognitive and biochemical alterations in ovariectomized rats treated with D-galactose. Folia Histochemica Et Cytobiologica, 53(4), 283-293.

Guo, Z., Chen, Y., Mao, Y-F., Zheng, T., Jiang, Y., Yan, Y., Yin, X., & Zhang, B. (2017). Long-term treatment with intranasal insulin ameliorates cognitive impairment, tau hyperphosphorilation, and microglial activation in a streptozocin-induced Alzheimer’s rat model. Scientific Reports, 7(45971), 01-12.

Joy, T., Rao, M. S., & Madhyastha, S. (2018). N-Acetyl Cysteine Supplement Minimize Tau Expression and Neuronal Loss in Animal Model of Alzheimer’s Disease. Brain Sciences, 8(10), 02-15, 2018.

Kocahan, S. & Doğan, Z. (2017). Mechanisms of Alzheimer’s Disease Pathogenesis and Prevention: The Brain, Neural Pathology, N-methyl-D-aspartate Receptors, Tau Protein and Other Risk Factors. Clinical Psychopharmacology and Neuroscience, 15(1), 01-08.

Korolev, I. O. (2014). Alzheimer’s disease: A Clinical and Basic Science Review. Medical Student Research Journal, 4(Fall), 24-33.

Lidsky, T. I. (2014). Is the Aluminum Hypothesis Dead? Journal of Occupational and Environmental Medicine, 56(5S), S73-S79.

Lu, C., Wang, Y., Xu, T., Li, Q., Wang, D., Zhang, L., Fan, B., Wang, F., & Liu, X. (2018). Genistein Ameliorates Scopolamine-Induced Amnesia in Mice Through the Regulation of the Cholinergic Neurotransmission, Antioxidant System and the ERK/CREB/BDNF Signaling. Frontiers of Pharmacology, 9(1153), 01-11.

Ma, L., Xiao, H. Wen, J., Liu, Z. He, Y., & Yuan, F. (2018). Possible mechanism of Vitis vinifera L. Lipids in Health and Disease, 17(152), 01-09.

Mahaman, Y. A. R., Huang, F., Wu, M., Wang, Y., Wei, Z., Bao, J., Salissou, M. T. M., Ke, D., Wang Q., Liu, R., Wang, J-Z., Zhang, B., Chen, D., & Wang, X. (2018). Moringa Oleifera Alleviates Homocysteine-Induced Alzheimer’s Disease-Like Pathology and Cognitive Impairments. Journal of Alzheimer’s Disease, 63(3), 1141-1159.

More, S. V., Kumar, H., Cho, D-Y., Yun, Y-S., & Choi, D-K. (2016). Toxin-Induced Experimental Models of Learning and Memory Impairment. International Journal of Molecular Sciences, 17(1447), 01-34.

Moreira-Silva, D., Carrettiero, D. C., Oliveira, A. S. A., Rodrigues, S., Santos-Lopes, J., Canas, P. M., Cunha, R. A., Almeida, M. C., & Ferreira, T. L. (2018). Anandamide Effects in a Streptozocin-Induced Alzheimer’s Disease-Like Sporadic Dementia in Rats. Frontiers in Neuroscience, 12(653), 01-14.

Morris, R. G. M., Garrud, P. Rawlins J. N. P., & O’Keefe, J. (1982). Place navigation impaired in rats with hippocampal lesions. Nature, 297, 681-683.

Munoz, D. G., & Feldman, H. (2000). Causes of Alzheimer’s Disease. Canadian Medical Association Journal, 162(1), 65-72.

Nazem, A., Sankowski, R., Bacher, M., & Al-Abed, Y. (2015). Rodent models of neuroinflammation for Alzheimer’s disease. Journal of Neuroinflammation, 12(74), 01-15.

Ohyagi, Y., & Miyoshi, K. (2013). Aluminum and Alzheimer’s Disease: An Update. Alzheimer’s Disease & Parkinsonism, 3(2), 01-07.

Parameshwaran, K., Irwin, M. H., Steliou, K., & Pinkert, C. A. (2010). D-Galactose Effectiveness in Modeling Aging and Therapeutic Antioxidant Treatment in Mice. Rejuvenation Research, 13(6), 729-735.

Petrasek, T., Skurlova, M., Maleninska, K., Vojtechova, I., Kristofikova, Z., Matuskova, H., Sirova, J., Vales, K., Ripova, D., & Stuchlik, A. (2016). A Rat Model of Alzheimer’s Disease Based on Abeta42 and Pro-oxidative Substances Exhibits Cognitive Deficit and Alterations in Glutamatergic and Cholinergic Neurotransmitter Systems. Frontiers in Aging Neuroscience, 8(93), 01-12.

Sachdev, P. (2004). Homocisteína e transtornos psiquiátricos. Revista Brasileira de Psiquiatria, 26(1), 50-56.

Singh, N. A., Bhardwaj, V., Ravi, C., Ramesh, N., Mandal, A. K. A., & Khan, Z. A. (2018). EGCG Nanoparticles Attenuate Aluminum Chloride Induced Neurobehavioral Deficits, Beta Amyloid and Tau Pathology in a Rat Model of Alzheimer’s Disease. Frontiers in Aging Neuroscience, 10(244), 01-13.

Torres, K. C. L., Santos, R. R., Mapal, F. C., Moraes, F. L., Moraes, E. N., & Silva, M. A. R. (2012). Biomarcadores na doença de Alzheimer. Geriatria & Gerontologia, 6(3), 273-282.

United Nations, Department of Economic and Social Affairs, & Population Division. (2017). World Population Prospects: The 2017 Revision, key Findings and Advanced Tables. Working Paper nº ESA/P/WP/248.

Vale, F. A. C., Neto, Y. C., Bertolucci, P. H. F., Machado, J. C. B., Silva, D. J., Allam, N., & Balthazar, M. L. F. (2011). Tratamento da doença de Alzheimer. Dementia e Neuropsychologia, 5(1), 34-48.

Vilaça, C. O., Freitas, M. R. G., Nascimento, O. J. M., Orsini, M., Leite, M. A. A., & Souza, J. A. (2015). Metabolismo da homocisteína em doenças neurológicas. Revista Brasileira de Neurologia, 51(3),73-78.

Walton, J. R. (2012). Cognitive Deterioration and Associated Pathology Induced by Chronic Low Level Aluminum Ingestion in a Translational Rat Model Provides an Explanation of Alzheimer’s Disease Tests for Susceptibility and Avenues for Treatment. International Journal of Alzheimer’s disease, 2012(914947), 01-17.

Zeng, K., Li, M., Hu, J., Mahaman Y. A. R., Bao J., Huang, F., Xia, Y., Liu, X., Wang, Q., Wang, J. Z., Yang Y., Liu R., & Wang X. (2018). Ginkgo biloba Extract EGb761 Attenuates Hyperhomocysteinemia-induced AD Like Tau Hyperphosphorylation and cognitive Impairment in Rats. Current Alzheimer Research, 15(1), 89-99.

Zidan, M., Arcoverde, C., Araújo, N. B., Vasques, P., Rios, A., Laks, J., & Deslandes, A. (2012). Alterações motoras e funcionais em diferentes estágios da doença de Alzheimer. Revista de Psiquiatria Clínica, 39(5), 161-165.



How to Cite

CORDEIRO, R. B.; TICLI, F. K.; CAVALLET, M. Substances administered for the induction of Alzheimer’s disease in rats. Research, Society and Development, [S. l.], v. 8, n. 6, p. e486974, 2019. DOI: 10.33448/rsd-v8i6.974. Disponível em: Acesso em: 16 oct. 2021.



Review Article