Towards the Prevention of Potential Aluminum Toxic Effects and an Effective Treatment for Alzheimer's Disease

Overview

Journal J Inorg Biochem

Specialty Biochemistry

Date 2011 Nov 22

PMID 22099160

Citations 22

Authors

Maire E Percy

Theo P A Kruck

Aileen I Pogue

Walter J Lukiw

Affiliations

Soon will be listed here.

Abstract

In 1991, treatment with low dose intramuscular desferrioxamine (DFO), a trivalent chelator that can remove excessive iron and/or aluminum from the body, was reported to slow the progression of Alzheimer's disease (AD) by a factor of two. Twenty years later this promising trial has not been followed up and why this treatment worked still is not clear. In this critical interdisciplinary review, we provide an overview of the complexities of AD and involvement of metal ions, and revisit the neglected DFO trial. We discuss research done by us and others that is helping to explain involvement of metal ion catalyzed production of reactive oxygen species in the pathogenesis of AD, and emerging strategies for inhibition of metal-ion toxicity. Highlighted are insights to be considered in the quests to prevent potentially toxic effects of aluminum toxicity and prevention and intervention in AD.

Citing Articles

Co-exposure to Aluminium and Cadmium Mediates Postpartum Maternal Variation in Brain Architecture and Behaviour of Mice; Involvement of Oxido-nitrergic and Cholinergic Mechanisms : Postpartum effects of Aluminium and Cadmium co-exposure in pregnancy.

Ichipi-Ifukor P, Asagba S, Achuba F Biol Trace Elem Res. 2024; 203(2):986-999.

PMID: 38777875 DOI: 10.1007/s12011-024-04218-0.

Long-Term Temporospatial Complementary Relationship between Degradation and Bone Regeneration of Mg-Al Alloy.

Chen L, Yan Z, Qiu T, Zhu J, Liu G, Han J ACS Appl Bio Mater. 2023; 6(11):4703-4713.

PMID: 37865928 PMC: 10664755. DOI: 10.1021/acsabm.3c00488.

Dietary Trace Elements and the Pathogenesis of Neurodegenerative Diseases.

Kawahara M, Kato-Negishi M, Tanaka K Nutrients. 2023; 15(9).

PMID: 37432185 PMC: 10180548. DOI: 10.3390/nu15092067.

Is heart disease a risk factor for low dementia test battery scores in older persons with Down syndrome? Exploratory, pilot study, and commentary.

Percy M, Lukiw W Int J Dev Disabil. 2021; 66(1):22-35.

PMID: 33859818 PMC: 8046177. DOI: 10.1080/20473869.2017.1301023.

Early insight into the potential contribution of aluminum to neurodegeneration - A tribute to the research work of Robert D. Terry, Igor Klatzo, Henryk M. Wisniewski and Donald R.C. Mclachlan.

Hill J, Percy M, Lukiw W J Inorg Biochem. 2019; 203:110860.

PMID: 31698325 PMC: 7012681. DOI: 10.1016/j.jinorgbio.2019.110860.

References

Exley C, Mamutse G, Korchazhkina O, Pye E, Strekopytov S, Polwart A . Elevated urinary excretion of aluminium and iron in multiple sclerosis. Mult Scler. 2006; 12(5):533-40. DOI: 10.1177/1352458506071323. View

McGeer E, McGeer P . Neuroinflammation in Alzheimer's disease and mild cognitive impairment: a field in its infancy. J Alzheimers Dis. 2010; 19(1):355-61. DOI: 10.3233/JAD-2010-1219. View

Li C, Wang J, Zhou B . The metal chelating and chaperoning effects of clioquinol: insights from yeast studies. J Alzheimers Dis. 2011; 21(4):1249-62. DOI: 10.3233/jad-2010-100024. View

Jomova K, Valko M . Advances in metal-induced oxidative stress and human disease. Toxicology. 2011; 283(2-3):65-87. DOI: 10.1016/j.tox.2011.03.001. View

Corrigan F, Pham C, Vink R, Blumbergs P, Masters C, Van Den Heuvel C . The neuroprotective domains of the amyloid precursor protein, in traumatic brain injury, are located in the two growth factor domains. Brain Res. 2011; 1378:137-43. DOI: 10.1016/j.brainres.2010.12.077. View

Levesque L, Mizzen C, McLachlan D, Fraser P . Ligand specific effects on aluminum incorporation and toxicity in neurons and astrocytes. Brain Res. 2000; 877(2):191-202. DOI: 10.1016/s0006-8993(00)02637-8. View

Amieva H, Stoykova R, Matharan F, Helmer C, Antonucci T, Dartigues J . What aspects of social network are protective for dementia? Not the quantity but the quality of social interactions is protective up to 15 years later. Psychosom Med. 2010; 72(9):905-11. DOI: 10.1097/PSY.0b013e3181f5e121. View

Da Costa R, Szyper-Kravitz M, Szekanecz Z, Csepany T, Danko K, Shapira Y . Ferritin and prolactin levels in multiple sclerosis. Isr Med Assoc J. 2011; 13(2):91-5. View

Exley C . The pro-oxidant activity of aluminum. Free Radic Biol Med. 2004; 36(3):380-7. DOI: 10.1016/j.freeradbiomed.2003.11.017. View

10.

Bandyopadhyay S, Huang X, Lahiri D, Rogers J . Novel drug targets based on metallobiology of Alzheimer's disease. Expert Opin Ther Targets. 2010; 14(11):1177-97. PMC: 6677255. DOI: 10.1517/14728222.2010.525352. View

11.

Sano M, Ernesto C, Thomas R, Klauber M, Schafer K, Grundman M . A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med. 1997; 336(17):1216-22. DOI: 10.1056/NEJM199704243361704. View

12.

Rogers J, Randall J, Cahill C, Eder P, Huang X, Gunshin H . An iron-responsive element type II in the 5'-untranslated region of the Alzheimer's amyloid precursor protein transcript. J Biol Chem. 2002; 277(47):45518-28. DOI: 10.1074/jbc.M207435200. View

13.

Honjo K, van Reekum R, Verhoeff N . Alzheimer's disease and infection: do infectious agents contribute to progression of Alzheimer's disease?. Alzheimers Dement. 2009; 5(4):348-60. DOI: 10.1016/j.jalz.2008.12.001. View

14.

Kusbeci O, Miman O, Yaman M, Aktepe O, Yazar S . Could Toxoplasma gondii have any role in Alzheimer disease?. Alzheimer Dis Assoc Disord. 2010; 25(1):1-3. DOI: 10.1097/WAD.0b013e3181f73bc2. View

15.

Carson M, Thrash J, Walter B . The cellular response in neuroinflammation: The role of leukocytes, microglia and astrocytes in neuronal death and survival. Clin Neurosci Res. 2011; 6(5):237-245. PMC: 2630233. DOI: 10.1016/j.cnr.2006.09.004. View

16.

Alexandrov P, Zhao Y, Pogue A, Tarr M, Kruck T, Percy M . Synergistic effects of iron and aluminum on stress-related gene expression in primary human neural cells. J Alzheimers Dis. 2005; 8(2):117-27. DOI: 10.3233/jad-2005-8204. View

17.

Walton J . Functional impairment in aged rats chronically exposed to human range dietary aluminum equivalents. Neurotoxicology. 2008; 30(2):182-93. DOI: 10.1016/j.neuro.2008.11.012. View

18.

Percy M, Moalem S, Garcia A, Somerville M, Hicks M, Andrews D . Involvement of ApoE E4 and H63D in sporadic Alzheimer's disease in a folate-supplemented Ontario population. J Alzheimers Dis. 2008; 14(1):69-84. DOI: 10.3233/jad-2008-14107. View

19.

Zapatero M, Garcia de Jalon A, Pascual F, Calvo M, Escanero J, Marro A . Serum aluminum levels in Alzheimer's disease and other senile dementias. Biol Trace Elem Res. 1995; 47(1-3):235-40. DOI: 10.1007/BF02790122. View

20.

Weinberg E . The hazards of iron loading. Metallomics. 2010; 2(11):732-40. DOI: 10.1039/c0mt00023j. View