The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Login
EN
+7 (495) 482-4118
+7 (495) 482-4329
+8 800 250-18-12
  • (toll-free number for subscriptions)
    Mon-Fri from 10 a.m. to 6 p.m.

  • © 1998-2026
+7 (495) 482-43-29
EN
All journals
Journal
Year
Year
Search result: 0

Salkov V.N.

Scientific Center of Neurology

Khudoyerkov R.M.

Scientific Center of Neurology

The role of aluminum and lead in the development of Alzheimer’s and Parkinson’s diseases

Authors:

Salkov V.N., Khudoyerkov R.M.

More about the authors

Journal: Russian Journal of Archive of Pathology. 2021;83(3): 56‑61

DOI: 10.17116/patol20218303156

Read: 10011 times

Contact the author
Table of contents

THE ROLE OF ALUMINUM AND LEAD IN THE DEVELOPMENT OF ALZHEIMER’S AND PARKINSON’S DISEASES
THE ROLE OF ALUMINUM AND LEAD IN THE DEVELOPMENT OF ALZHEIMER’S AND PARKINSON’S DISEASES

To cite this article:

Salkov VN, Khudoyerkov RM. The role of aluminum and lead in the development of Alzheimer’s and Parkinson’s diseases. Russian Journal of Archive of Pathology. 2021;83(3):56‑61. (In Russ.)
https://doi.org/10.17116/patol20218303156

Подписка 2026 Архив патологии (Russian Journal of Archive of Pathology)
МСФ на ЯМ
Использование инфографики авторами научных работ
Close metadata
Recommended articles:
Features of facial expressions in patients with cognitive impairment due to Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(7):104-109
Study of neurodegeneration in multiple scle­rosis using opti­cal cohe­rence tomo­graphy of the retina and magnetic reso­nance morphometry of the brain. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(7-2):66-72
Dyna­mics of permeability of the blood-brain barrier after FUS thalamotomy acco­rding to contrast-enhanced MRI. Burdenko's Journal of Neurosurgery. 2025;(4):51-60
Change of speech diso­rders during bila­teral deep stimulation of the subthalamic nucleus of the brain in patients with Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(8):59-65
Diagnosis of Alzheimer’s disease using biological markers in corticobasal syndrome. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(8):133-139
Oxidative stress and depression in Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(9):131-138
Current aspe­cts of the rela­tionship between depression and cognitive impairment in patients with Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(10):66-74
Musculoskeletal diso­rders in patients with Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(11-2):6-10
Sele­ction of patients with Parkinson’s disease for inte­rventional therapies: A review of available tools — scales and questionnaires. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(11-2):11-17
«Brain—gut—microbiome» axis in patients with Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(11-2):18-23
Abstract:

The article summarizes the data available in the literature on the toxic effects of aluminum and lead on the human brain and assesses the relationship of these effects to the etiopathogenesis of the most common neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. The accumulation of ions of these metals in the brain structures leads to chronic intoxication that is manifested by the morphological signs that are typical for Alzheimer’s disease, such as deposits of β-amyloid and τ-protein mainly in the frontal and temporal regions of the cortex, and for Parkinson’s disease, such as degeneration of dopamine neurons in the substantia nigra and their accumulation of α-synuclein. The most likely forms of participation of aluminum and lead ions in the mechanisms of neurodegeneration are the replacement of bivalent metal ions necessary for brain functioning, oxidative stress initiation, epigenetic modifications of histones, and increased expression of noncoding ribonucleic acids.

Keywords:

neurodegeneration
brain
aluminum
lead
Alzheimer’s disease
Parkinson’s disease

Authors:

Salkov V.N.

Scientific Center of Neurology

Khudoyerkov R.M.

Scientific Center of Neurology

Received:

26.01.2021

Accepted:

05.03.2021

Close metadata

References:

  1. Chin-Chan M, Navarro-Yepes J, Quintanilla-Vega B. Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Front Cell Neurosci. 2015;9:124.  https://doi.org/10.3389/fncel.2015.00124
  2. World Health Organization. Dementia: a public health priority. Geneva: World Health Organization; 2017.
  3. Ball N, Teo W-P, Chandra S, Chapman J. Parkinson’s disease and the environment. Front Neurol. 2019;10:218.  https://doi.org/10.3389/fneur.2019.00218
  4. Carboni E, Lingor P. Insights on the interaction of alpha-synuclein and metals in the pathophysiology of Parkinson’s disease. Metallomics. 2015;7(3):395-404.  https://doi.org/10.1039/c4mt00339j
  5. Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem. 2010; 345(1-2):91-104.  https://doi.org/10.1007/s11010-010-0563-x
  6. Li Y, Jiao Q, Xu H, Du X, Shi L, Jia F, Jiang H. Biometal dyshomeostasis and toxic metal accumulations in the development of Alzheimer’s disease. Front Mol Neurosci. 2017;10:339.  https://doi.org/10.3389/fnmol.2017.00339
  7. Gupta VB, Anitha S, Hegde ML, Zecca L, Garruto RM, Ravid R, Shankar SK, Stein R, Shanmugavelu P, Rao KSJ. Aluminium in Alzheimer’s disease: are we still at a crossroad? Cell Mol Life Sci. 2005;62(2):143-158.  https://doi.org/10.1007/s00018-004-4317-3
  8. Rondeau V, Jacqmin-Gadda H, Commenges D, Helmer C, Dartigues JF. Aluminum and silica in drinking water and the risk of Alzheimer’s disease or cognitive decline: findings from 15-year follow-up of the PAQUID cohort. Am J Epidemiol. 2009;169(4): 489-96.  https://doi.org/10.1093/aje/kwn348
  9. Altschuler E. Aluminum-containing antacids as a cause of idiopathic Parkinson’s disease. Med Hypotheses. 1999;53(1):22-23.  https://doi.org/10.1054/mehy.1997.0701
  10. Momcilović B, Alkhatib HA, Duerre JA, Cooley M, Long WM, Harris TR, Lykken GI. Environmental lead-210 and bismuth-210 accrue selectively in the brain proteins in Alzheimer disease and brain lipids in Parkinson disease. Alzheimer Dis Assoc Disord. 2001; 15(2):106-115.  https://doi.org/10.1097/00002093-200104000-00012
  11. Gunnarsson L-G, Bodin L. Occupational exposures and neurodegenerative diseases — a systematic literature review and meta-analyses. Int J Environ Res Public Health. 2019;16(3):337.  https://doi.org/10.3390/ijerph16030337
  12. Altmann P, Cunningham J, Dhanesha U, Ballard M, Thompson J, Marsh F. Disturbance of cerebral function in people exposed to drinking water contaminated with aluminium sulphate: retrospective study of the Camelford water incident. BMJ. 1999;319(7213): 807-811.  https://doi.org/10.1136/bmj.319.7213.807
  13. Flaten TP. Aluminium as a risk factor in Alzheimer’s disease, with emphasis on drinking water. Brain Res Bull. 2001;55(2):187-196.  https://doi.org/10.1016/s0361-9230(01)00459-2
  14. Shen XL, Yu JH, Zhang DF, Xie JX, Jiang H. Positive relationship between mortality from Alzheimer’s disease and soil metal concentration in mainland China. J Alzheimers Dis. 2014;42(3):893-900.  https://doi.org/10.3233/JAD-140153
  15. Fulgenzi A, Vietti D, Ferrero ME. Aluminium involvement in neurotoxicity. Biomed Res Int. 2014;2014:758323. https://doi.org/10.1155/2014/758323
  16. Lukiw WJ, Kruck ThPA, Percy ME, Pogue AI, Alexandrov PN, Walsh WJ, Sharfman NM, Jaber VR, Zhao Yu, Li W, Bergeron C, Culicchia F, Fang ZH, McLachlan DRC. Aluminum in neurological disease — a 36 year multicenter study. J Alzheimers Dis Parkinsonism. 2019;8(6):457.  https://doi.org/10.4172/2161-0460.1000457
  17. Yumoto S, Kakimi S, Ohsaki A, Ishikawa A. Demonstration of aluminum in amyloid fibers in the cores of senile plaques in the brains of patients with Alzheimer’s disease. J Inorg Biochem. 2009;103(11):1579-1584. https://doi.org/10.1016/j.jinorgbio.2009.07.023
  18. Mocanu CS, Jureschi M, Drochioiu G. Aluminium binding to modified amyloid-β peptides: implications for Alzheimer’s disease. Molecules. 2020;25(19):4536. https://doi.org/10.3390/molecules25194536
  19. Kawahara M, Kato-Negishi M. Link between aluminum and the pathogenesis of Alzheimer’s disease: the integration of the aluminum and amyloid cascade hypotheses. Int J Alzheimers Dis. 2011;2011:276393. https://doi.org/10.4061/2011/276393
  20. Bolognin S, Messori L, Drago D, Gabbiani Ch, Cendron L, Zatta P. Aluminum, copper, iron and zinc differentially alter amyloid-Aβ(1-42) aggregation and toxicity. Int J Biochem Cell Biol. 2011;43(6):877-885.  https://doi.org/10.1016/j.biocel.2011.02.009
  21. Bader B, Nübling G, Mehle A, Nobile S, Kretzschmar H, Giese A. Single particle analysis of tau oligomer formation induced by metal ions and organic solvents. Biochem Biophys Res Commun. 2011;411(1):190-196.  https://doi.org/10.1016/j.bbrc.2011.06.135
  22. Sato N, Hori O, Yamaguchi A, Lambert JC, Chartier-Harlin MC, Robinson PA, Delacourte A, Schmidt AM, Furuyama T, Imaizumi K, Tohyama M, Takagi T. A novel presenilin-2 splice variant in human Alzheimer’s disease brain tissue. J Neurochem. 2002;72(6):2498-2505. https://doi.org/10.1046/j.1471-4159.1999.0722498.x
  23. Muckenthaler MU, Galy B, Hentze MW. Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu Rev Nutr. 2008;28(1):197-213.  https://doi.org/10.1146/annurev.nutr.28.061807.155521
  24. Crichton RR, Wilmet S, Legssyer R, Ward RJ. Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells. J Inorg Biochem. 2002;91(1):9-18.  https://doi.org/10.1016/s0162-0134(02)00461-0
  25. Walton JR, Wang MX. APP expression, distribution and accumulation are altered by aluminum in a rodent model for Alzheimer’s disease. J Inorg Biochem. 2009;103(11):1548-1554. https://doi.org/10.1016/j.jinorgbio.2009.07.027
  26. Duce JA, Tsatsanis A, Cater MA, James S, Robb E, Wikhe K, Leong S, Perez K, Johanssen T, Greenough M, Cho H, Galatis D, Moir R, Masters C, McLean C, Tanzi R, Cappai R, Barnham K, Ciccotosto G, Rogers J, Bush A. Iron-export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer’s disease. Cell. 2010;142(6):857-867.  https://doi.org/10.1016/j.cell.2010.08.014
  27. Kaneko N, Sugioka T, Sakurai H. Aluminum compounds enhance lipid peroxidation in liposomes: insight into cellular damage caused by oxidative stress. J Inorg Biochem. 2007;101(6):967-975.  https://doi.org/10.1016/j.jinorgbio.2007.03.005
  28. Zhao Y, Bhattacharjee S, Jones BM, Hill J, Dua P, Lukiw WJ. Regulation of neurotropic signaling by the inducible, NF-kB-sensitive miRNA-125b in Alzheimer’s disease (AD) and in primary human neuronal-glial (HNG) cells. Mol Neurobiol. 2014;50(1):97-106.  https://doi.org/10.1007/s12035-013-8595-3
  29. Lukiw WJ. NF-kappaB-regulated, proinflammatory miRNAs in Alzheimer’s disease. Alzheimers Res Ther. 2012;4(6):47.  https://doi.org/10.1186/alzrt150
  30. Good PF, Olanow CW, Perl DP. Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson’s disease: a LAMMA study. Brain Res. 1992;593(2):343-346.  https://doi.org/10.1016/0006-8993(92)91334-b
  31. Yasui M, Kihira T, Ota K. Calcium, magnesium and Al concentrations in Parkinson’s disease. Neurotoxicology. 1991;13(3):593-600. 
  32. Zatta P, Zambenedetti P, Milanese M. Activation of monoamine oxidase type-B by aluminum in rat brain homogenate. Neuroreport. 1999;10(17):3645-2648. https://doi.org/10.1097/00001756-199911260-00033
  33. Burke WJ, Kumar VB, Pandey N, Panneton WM, Gan Q, Franko MW, O’Dell M, Li SW, Pan Y, Chung HD, Galvin JE. Aggregation of alpha-synuclein by DOPAL, the monoamine oxidase metabolite of dopamine. Acta Neuropathol. 2008;115(2):193-203.  https://doi.org/10.1007/s00401-007-0303-9
  34. Uversky VN, Li J, Fink AL. Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson’s disease and heavy metal exposure. J Biol Chem. 2001;276(47):44284-44296. https://doi.org/10.1074/jbc.M105343200
  35. VanDuyn N, Settivari R, LeVora J, Zhou SH, Unrine J, Nass R. The metal transporter SMF-3/DMT-1 mediates aluminum-induced dopamine neuron degeneration. J Neurochem. 2013;124(1):147-157.  https://doi.org/10.1111/jnc.12072
  36. Iglesias-González J, Sánchez-Iglesias S, Beiras-Iglesias A, Méndez-Álvarez E, Soto-Otero R. Effects of aluminium on rat brain mitochondria bioenergetics: an in vitro and in vivo study. Mol Neurobiol. 2017;54(1):563-570.  https://doi.org/10.1007/s12035-015-9650-z
  37. Bharathi, Vasudevaraju P, Govindaraju M, Palanisamy AP, Sambamurti K, Rao KS. Molecular toxicity of aluminium in relation to neurodegeneration. Indian J Med Res. 2008;128(4):545-556. 
  38. Bondy SC. Low levels of aluminum can lead to behavioral and morphological changes associated with Alzheimer’s disease and age-related neurodegeneration. Neurotoxicology. 2016;52:222-229.  https://doi.org/10.1016/j.neuro.2015.12.002
  39. Bhat AH, Dar KB, Anees S, Zargar MA, Masood A, Sofi MA, Ganie SA. Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother. 2015;74:101-110.  https://doi.org/10.1016/j.biopha.2015.07.025
  40. Tamegart L, Abbaoui A, Makbal R, Zroudi M, Bouizgarne B, Bouyatas MM, Gamrani H. Crocus sativus restores dopaminergic and noradrenergic damages induced by lead in Meriones shawi: A possible link with Parkinson’s disease. Acta Histochem. 2019;12(2):171-181.  https://doi.org/10.1016/j.acthis.2018.12.003
  41. Liu F, Xue Z, Li N, Huang H, Ying Y, Li J, Wang L, Li W. Effects of lead exposure on the expression of amyloid beta and phosphorylated tau proteins in the C57BL/6 mouse hippocampus at different life stages. J Trace Elem Med Biol. 2014;28(2):227-232.  https://doi.org/10.1016/j.jtemb.2014.01.002
  42. Basha MR, Wei W, Bakheet SA, Benitez N, Siddiqi HK, Ge YW, Lahiri DK, Zawia NH. The fetal basis of amyloidogenesis: exposure to lead and latent overexpression of amyloid precursor protein and beta-amyloid in the aging brain. J Neurosci. 2005;25(4):823-829.  https://doi.org/10.1523/JNEUROSCI.4335-04.2005
  43. Ashok A, Rai NK, Tripathi S, Bandyopadhyay S. Exposure to As-, Cd- and Pb-mixture induces Aβ, amyloidogenic APP processing and cognitive impairments via oxidative stress-dependent neuroinflammation in young rats. Toxicol Sci. 2015;143(1):64-80.  https://doi.org/10.1093/toxsci/kfu208
  44. Wu J, Basha MR, Brock B, Cox DP, Cardozo-Pelaez F, McPherson CA, Harry J, Rice DC, Maloney B, Chen D, Lahiri DK, Zawia NH. Alzheimer’s disease (AD)-like pathology in aged monkeys after infantile exposure to environmental metal lead (Pb): Evidence for a developmental origin and environmental link for AD. J Neurosci. 2008;28(1):3-9.  https://doi.org/10.1523/JNEUROSCI.4405-07.2008
  45. Wu S, Liu H, Zhao H, Wang X, Chen J, Xia D, Xiao C, Cheng J, Zhao Z, He Y. Environmental lead exposure aggravates the progression of Alzheimer’s disease in mice by targeting on blood brain barrier. Toxicol Lett. 2020;319:138-147.  https://doi.org/10.1016/j.toxlet.2019.11.009
  46. Fathabadi B, Dehghanifiroozabadi M, Aaseth J, Sharifzadeh G, Nakhaee S, Rajabpour-Sanati A, Amirabadizadeh A, Mehrpour O. Comparison of blood lead levels in patients with Alzheimer’s disease and healthy people. Am J Alzheimers Dis Other Demen. 2018;33(8):541-547.  https://doi.org/10.1177/1533317518794032
  47. Horton CJ, Weng HY, Wells EM. Association between blood lead level and subsequent Alzheimer’s disease mortality. Environ Epidemiol. 2019;3(3):e045. https://doi.org/10.1097/EE9.0000000000000045
  48. Gerhardsson L, Lundh T, Minthon L, Londos E. Metal concentrations in plasma and cerebrospinal fluid in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord. 2008;25(6):508-515.  https://doi.org/10.1159/000129365
  49. Kern M, Wisniewski M, Cabell L, Audesirk G. Inorganic lead and calcium interact positively in activation of calmodulin. Neurotoxicology. 2000;21(3):353-363. 
  50. Trakhtenberg IM. Kniga o yadakh i otravleniyakh: ocherki toksikologii. Kiev: Naukova Dumka; 2003. (In Russ.).
  51. Wang T, Zhang J, Xu Y. Epigenetic basis of lead-induced neurological disorders. Int J Environ Res Public Health. 2020;17(13):4878. https://doi.org/10.3390/ijerph17134878
  52. Bihaqi SW, Huang H, Wu J, Zawia NH. Infant exposure to lead (Pb) and epigenetic modifications in the aging primate brain: Implications for Alzheimer’s disease. J Alzheimers Dis. 2011;27(4):819-833.  https://doi.org/10.3233/JAD-2011-111013
  53. Coon S, Stark A, Peterson E, Gloi A, Kortsha G, Pounds J, Chettle D, Gorell J. Whole-body lifetime occupational lead exposure and risk of Parkinson’s disease. Environ Health Perspect. 2006; 114(12):1872-1876. https://doi.org/10.1289/ehp.9102
  54. Weisskopf MG, Weuve J, Nie H, Saint-Hilaire MH, Sudarsky L, Simon DK, Hersh B, Schwartz J, Wright RO, Hu H. Association of cumulative lead exposure with Parkinson’s disease. Environ Health Perspect. 2010;118(11):1609-1613. https://doi.org/10.1289/ehp.1002339
  55. Kala SV, Jadhav AL. Low level lead exposure decreases in vivo release of dopamine in the rat nucleus accumbens: a microdialysis study. J Neurochem. 1995;65(4):1631-1635. https://doi.org/10.1046/j.1471-4159.1995.65041631.x
  56. Tavakoli-Nezhad M, Pitts DK. Postnatal inorganic lead exposure reduces midbrain dopaminergic impulse flow and decreases dopamine D1 receptor sensitivity in nucleus accumbens neurons. J Pharmacol Exp Ther. 2005;312:1280-1288. https://doi.org/10.1124/jpet.104.076166
  57. Sandhir R, Julka D, Gill KD. Lipoperoxidative damage on lead exposure in rat brain and its implications on membrane bound enzymes. Pharmacol Toxicol. 1994;74(2):66-71.  https://doi.org/10.1111/j.1600-0773.1994.tb01077.x
  58. Yamin G, Glaser CB, Uversky VN, Fink AL. Certain metals trigger fibrillation of methionine-oxidized alpha-synuclein. J Biol Chem. 2003;278(30):27630-27635. https://doi.org/10.1074/jbc.m303302200
  59. Zhang J, Cai T, Zhao F, Yao T, Chen Y, Liu X, Luo W, Chen J. The role of alphasynuclein and tau hyperphosphorylation-mediated autophagy and apoptosis in lead-induced learning and memory injury. Int J Biol Sci. 2012;8(7):935-944.  https://doi.org/10.7150/ijbs.4499
  60. Jowaed A, Schmitt I, Kaut O, Wullner U. Methylation regulates alpha-synuclein expression and is decreased in Parkinson’s disease patients’ brains. J Neurosci. 2010;30(18):6355-6259. https://doi.org/10.1523/JNEUROSCI.6119-09.2010
  61. Gebremedhin KG, Rademacher DJ. Histone H3 acetylation in the postmortem Parkinson’s disease primary motor cortex. Neurosci Lett. 2016;627:121-125.  https://doi.org/10.1016/j.neulet.2016.05.060
Contact the author
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

Contact us
If you have any questions, complaints or suggestions, please use this feedback form.
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.
Submit Application

You can become an author of one of our magazines, send a request and we will consider it in during the day.

Name
Phone
E-mail
Message
Login
Registration
E-mail
Password
Forgot Password?

Log in to the site using your account in one of the services

Password recovery
E-mail
Login
Register

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.