Type of Article:  Original Research

Volume 11; Issue 2 (June2023)

Page No.: 8610-8618

DOI: https://dx.doi.org/10.16965/ijar.2023.106

Role of Aluminium in Alzheimer’s disease: Ultrastructural Study in Rat Hippocampus

Buddhadeb Ghosh *1, Akhtaruzzaman 2, Shukchand Hansda 3, Suman Yadav 4, Ravi Kant Sharma 5.

*1 Department of Anatomy, Apollo Institute of Medical Science & Research, Hyderabad, India. ORCiD: 0000-0001-8688-3817

2 Department of Anatomy, Jalpaiguri Government Medical College & Hospital, West Bengal, India. ORCiD: 0000-0002-5843-3904

3 Department of Anatomy, Institute of Post Graduate Medical Education & Research, Kolkata, West Bengal, India. ORCiD: 0000-0002-6819-9904

4 Department of Anatomy, Dr Rajendra Prasad Government Medical College, Kangra, Himachal Pradesh, India. ORCiD: 0009-0004-7902-6381

4 Department of Anatomy, Government Medical College, Amritsar, Punjab, India.

Corresponding Author: Dr. Buddhadeb Ghosh, Department of Anatomy, Apollo Institute of Medical Science & Research, Hyderabad, India. Mob +918894114210.
dr.ghosh_b@apolloimsr.edu.in / dr.ghosh86@gmail.com


Background: Exposure to high levels of aluminium (Al) leads to neurotoxicity. Hippocampus is one of the preferred sites of aluminium accumulation. Nevertheless, the role of Al in Alzheimer’s disease (AD) remains controversial and there is little proof directly interlinking Al to AD.

Aims: The present study was undertaken to find out the occurrence of AD pathogenesis in Hippocampus under moderate aluminium exposure in rats.

Materials and Methods: Adult rats were divided into control (C) and aluminium treated (E) groups having eight animal each. The rats in group E were exposed to aluminium 4.2 mg/kg body weight for three months with due approval from Institute Animal Ethics Committee. The hippocampus was processed for histopathological and electron microscopy observation.

Results: Moderate Al intake produces significant reduction in the count of Pyramidal cells in hippocampus identified by shrunken cells as well as pyknosis in cell bodies. The differences between the cell numbers in all groups were found to be statistically significant (P < 0.05).  Cornu Ammonis (CA) exhibited significantly reduced nissl bodies with a marked reduction in neuronal cell loss. Neurofibrillary tangle and plaques were not seen in the given dose of Al exposure. Electron microscopy from experimental group showed that the majority of neurons were disintegrating, the nuclear membrane has ruptured, and nucleoli appeared significantly distorted. The chromatin condensed and the mitochondria had disintegrated. Many vacuoles and lipofuscin sediment in cytoplasm, as compared to the control group noted.

Conclusion: Present data demonstrated that moderate chronic aluminium exposure 4.2mg/kg body weight induced neurodegeneration in hippocampus but not significant for Alzheimer’s disease pathogenesis.

Keywords: Aluminium, Hippocampus, Alzheimer’s Disease, Neurodegeneration, Histopathology, Electron microscopy.


[1]. Nayak P, Sharma SB, Chowdary NV. Augmentation of aluminium-induced oxidative stress in rat cerebrum by presence of pro-oxidant (graded doses of ethanol) exposure. Neurochem Res 2010; 35(11):1681-90. https://doi:org/10.1007/s11064-010-0230-3.
[2]. Ghosh B, Sharma, RK, Yadav S. Aluminium Induced Neurodegeneration in Rat Cerebellum in the Presence of Ethanol Coexposure. Journal of Pharmacy and Bio-allied Science 2021; 13(6):S1228-33. https://doi: 10.4103/jpbs.jpbs_377_21.PMCID: PMC8687035. PMID: 35017961
[3]. Karbouj R. Aluminium leaching using chelating agents as compositions of food. Food Chem Toxicol 2007; 45(9):1688-93. https://doi:org/10.1016/j.fct.2007.03.001.
[4]. Rao KS J, Valeswara Rao G. Aluminium leaching from utensils – a kinetic study. Int J Food Sci Nutr 1995;46: 31-8. https://doi:org/10.3109/09637489509003383.
[5]. Akay C, Kalman S, Dundaroz R, Sayal A, Aydin A, Ozkan Y, Gul H. Serum aluminium levels in glue-sniffer adolescent and in glue containers. Basic Clin Pharmacol Toxicol 2008;102(5):433-6. https://doi:org/10.1111/j.1742-7843.2008.00226.x. PMID: 18331391
[6]. Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis. Cell 2008;22;132(4):645-60. https://doi:org/10.1016/j.cell.2008.01.033. PMID: 18295581
[7]. Savory J, Herman MM, Ghribi O. Mechanisms of aluminum-induced neurodegeneration in animals: Implications for Alzheimer’s disease. J Alzheimers Dis 2006; 10(2-3):135-44. https://doi:org/10.3233/jad-2006-102-302. PMID: 17119283.
[8]. Dumont M. Behavioural phenotyping of mouse models of neurodegeneration. Methods Mol Biol 2011;793:229-37. https://doi:org/10.1007/978-1-61779-328-8_15. PMID: 21913104.
[9]. Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL. Alzheimer’s disease: cell-specific pathology isolates the hippocampal formation. Science 1984; 14(225):1168-70. https://doi:org/10.1126/science.6474172. PMID: 6474172.
[10]. Bancroft JD, Cook HC. Manual of Histological Techniques. Edinburgh Churchill Livingstone 1984; 201-202. https://doi.org/10.1002/path.1711450410.
[11]. Mooradian AD. Effect of aging on the blood-brain barrier. Neurobiol Aging 1998; 9(1):31-9. https://doi:org/10.1016/s0197-4580(88)80013-7. PMID: 3288893.
[12]. Ghosh B, Sharma RK, Yadav S, Parashar V, Jagdish P. Ethanol Exposure Induces Cerebellar Neuronal Loss in Rats. Eur. J. Anat 2020;24(5):407-413. https://eurjanat.com/v1/data/pdf/eja.200181bg.pdf
[13]. Yan D, Jin C, Cao Y, Wang L, Lu X, Yang J, Wu S, Cai Y. Effects of Aluminium on Long-Term Memory in Rats and on SIRT1 Mediating the Transcription of CREB-Dependent Gene in Hippocampus. Basic Clin Pharmacol Toxicol 2017;121(4):342-352. https://doi:org/10.1111/bcpt.12798. PMID: 28429887.
[14]. Walton JR. Aluminium involvement in the progression of Alzheimer’s disease. J Alzheimers Dis 2013; 35(1):7-43. https://doi:org/10.3233/JAD-121909. PMID: 23380995.
[15]. Andrasi E, Pali N, Molnar Z, Kosel S. Brain aluminum, magnesium and phosphorus contents of control and Alzheimer-diseased patients. J Alzheimers Dis 2005;7(4):273-84. https://doi:org/10.3233/jad-2005-7402. PMID: 16131728.
[16]. Deloncle R, Guillard O. Mechanism of Alzheimer’s disease: arguments for a neurotransmitter-aluminium complex implication. Neurochem Res 1990; 15 (12): 1239–1245. https://doi.org/10.1007/BF01208586.
[17]. Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, Delon MR. Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 1982; 215(4537):1237-9. https://doi:org/10.1126/science.7058341. PMID: 7058341.
[18]. Kaneko N, Yasui H, Takada J, Suzuki K, Sakurai H. Orally administrated aluminium-maltolate complex enhances oxidative stress in the organs of mice. J Inorg Biochem 2004;98(12):2022-31. https://doi:org/10.1016/j.jinorgbio.2004.09.008. PMID: 15541491.
[19]. Garruto RM, Fukatsu R, Yanagihara R, Gajdusek DC, Hook G, Fiori CE. Imaging of calcium and aluminum in neurofibrillary tangle-bearing neurons in parkinsonism-dementia of Guam. Proc Natl Acad Sci U S A 1984;81(6):1875-9. https://doi:org/10.1073/pnas.81.6.1875. PMID: 6584922;
[20]. Katsetos CD, Savory J, Herman MM, Carpenter RM, Frankfurter A, Hewitt CD, Wills MR. Neuronal cytoskeletal lesions induced in the CNS by intraventricular and intravenous aluminium maltol in rabbits. Neuropathol Appl Neurobiol 1990;16(6):511-28. https://doi:org/10.1111/j.1365-2990.1990.tb01290.x. PMID: 2096317.
[21]. Yokel RA. Aluminum produces age related behavioral toxicity in the rabbit. Neurotoxicol Teratol 1989; 11(3):237-42. https://doi:org/10.1016/0892-0362(89)90065-2. PMID: 2755420
[22]. Mclachlan DR, Kruck TP, Lukiw WJ, Krishnan SS. Would decreased aluminium ingestion reduce the incidence of Alzheimer’s disease? CMAJ 1991;145(7):793-804. PMID: 1822096; PMCID: PMC1335899.
[23]. Muller JP, Bruinink A. Neurotoxic effects of aluminium on embryonic chick brain cultures. Acta Neuropathol 1994; 88(4):359-66. https://doi:org/10.1007/BF00310380. PMID: 7839829
[24]. Hermenegildo C, Saez R, Minoia C, Manzo L, Felipo V. Chronic exposure to aluminium impairs the glutamate-nitric oxide-cyclic GMP pathway in the rat in vivo. Neurochem Int 1999; 34(3): 245–253. https://doi:org/10.1016/s0197-0186(99)00010-8. PMID: 10355491
[25]. Miu Ac, Benga O. Aluminum and Alzheimer’s disease: a new look. J Alzheimers Dis 2006;10(2-3):179-201. https://doi:org/10.3233/jad-2006-102-306. PMID: 17119287.
[26]. Zhang L, Jin C, Liu Q, Lu X, Wu S, Yang J. Effects of subchronic aluminum exposure on spatial memory, ultrastructure and L-LTP of hippocampus in rats. J Toxicol Sci 2013;38:255–68. https://doi:org/10.2131/jts.38.255. PMID: 23535404
[27]. Akinrinade Id, Memudu Ae, Ogundele Om. Fluoride and aluminium disturb neuronal morphology, transport functions, cholinesterase, lysosomal and cell cycle activities. Pathophysiology 2015; 22(2):105-15. https://doi:org/10.1016/j.pathophys.2015.03.001. PMID: 25863844.
[28]. Klotz K, Weistenhofer W, Neff F, Hartwig A, Van Thriel C, Drexler H. The Health Effects of Aluminum Exposure. Dtsch Arztebl Int 2017; 114(39):653-659. https://doi:org/10.3238/arztebl.2017.0653. PMID: 29034866; PMCID: PMC5651828.
[29]. Walton JR. Cognitive deterioration and associated pathology induced by chronic low-level aluminium ingestion in a translational rat model provides an explanation of Alzheimer’s disease, tests for susceptibility and avenues for treatment. Int J Alzheimers Dis 2012; 914-947. https://doi.org/10.2131/jts.38.255.

Cite this article: Buddhadeb Ghosh, Akhtaruzzaman, Shukchand Hansda, Suman Yadav, Ravi Kant Sharma. Role of Aluminium in Alzheimer’s disease: Ultrastructural Study in Rat Hippocampus. Int J Anat Res 2023;11(2):8610-8618. DOI: 10.16965/ijar.2023.106