The Role of Iron, Copper and Zinc Elements in the Pathogenesis of Alzheimer's Disease

Yıl 2022, Cilt: 3 Sayı: 1, 13 - 17, 30.06.2022

İpek Aydın İrem Gülfem Albayrak Seda Kuşoğlu Belkis Atasever Arslan

Öz

The clinical syndrome that prevents individuals from living a functional and independent life due to impairments in various cognitive areas is called dementia. The most common cause of dementia is Alzheimer's disease. Alzheimer's disease is very common worldwide and mortality rates due to Alzheimer's disease are very high. Age is the most important risk factor for Alzheimer's disease. In addition to the medical history, laboratory tests and physical examination for the diagnosis of Alzheimer's disease; brain imaging techniques such as positron emission tomography and electroencephalography are used. Alzheimer's disease is a chronic neurodegenerative disease characterized histopathologically by the presence of amyloid-β peptides in extracellular senile plaques and the formation of intracellular neurofibrillary tangles. Trace elements are associated with the formation of amyloid-β plaques and play an important role in the progression of Alzheimer's disease.
It is thought that the deterioration in metal homeostasis may be a cause of Alzheimer's disease. It was determined that amyloid-β misfolding was significantly affected by the presence of metals both in and around the established Alzheimer's disease plaques. The presence of copper, iron, and zinc in amyloid-β clusters has been recently associated with neurotoxicity. In addition, it has been shown that the redox activity of metal ions can trigger cellular cascades that leads to the production of reactive oxygen species. Studies have shown that restoring the proper metal ion balance in the brain can stop amyloid-β aggregation, break up amyloid plaques, and slow down the cognitive decline associated with Alzheimer's disease in patients with Alzheimer's disease.
In this review study, the effect of metal ions on Alzheimer's disease is discussed in the light of current studies in the literature.

Anahtar Kelimeler

Alzheimer’s disease, copper, zinc, iron.

Kaynakça

• [1] G. M. McKhann et al., “The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease,” Alzheimers. Dement., vol. 7, no. 3, pp. 263–269, 2011.
• [2] Y. Ozer, F. Ozen, Y. Diler, A. D. Yalcin, and B. Atasever-Arslan, “Proteasome modulator 9 (PSMD9) gene rs14259 polymorphism in Alzheimer’s disease,” Bratislava Med. J., vol. 121, no. 5, pp. 331–333, 2020.
• [3] W. W. Barker et al., “Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank,” Alzheimer Dis. Assoc. Disord., vol. 16, no. 4, pp. 203–212, Oct. 2002.
• [4] Alzheimer, Association, sciencestaff, and alzorg, “2019 Alzheimer’s disease facts and figures,” John Wiley & Sons, Ltd, Mar. 2019.
• [5] C. R. Jack et al., “NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease,” Alzheimers. Dement., vol. 14, no. 4, pp. 535–562, Apr. 2018.
• [6] A. Serrano-Pozo, M. P. Frosch, E. Masliah, and B. T. Hyman, “Neuropathological alterations in Alzheimer disease,” Cold Spring Harb. Perspect. Med., vol. 1, no. 1, Sep. 2011.
• [7] B. Atasever-Arslan, Y. Ozer, F. Ozen, Y. Diler, and A. D. Yalcin, “Tumor necrosis factor alpha gene rs1799724 polymorphism in alzheimer’s disease,” Gen. Physiol. Biophys., vol. 39, no. 6, pp. 595–599, Nov. 2020.
• [8] S. Takeda, “Tau Propagation as a Diagnostic and Therapeutic Target for Dementia: Potentials and Unanswered Questions,” Front. Neurosci., vol. 13, p. 1274, Dec. 2019.
• [9] P. T. Nelson et al., “Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature,” J. Neuropathol. Exp. Neurol., vol. 71, no. 5, pp. 362–381, May 2012.
• [10] C. R. Jack et al., “Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers,” Lancet. Neurol., vol. 12, no. 2, pp. 207–216, Feb. 2013.
• [11] R. U. Haque and A. I. Levey, “Alzheimer’s disease: A clinical perspective and future nonhuman primate research opportunities,” Proc. Natl. Acad. Sci. U. S. A., vol. 116, no. 52, pp. 26224–26229, Dec. 2019.
• [12] S. D. La Monte, “Alzheimer’s Disease Pathogenesis - Core Concepts, Shifting Paradigms and Therapeutic Targets,” Alzheimer’s Dis. Pathog. Concepts, Shifting Paradig. Ther. Targets, Sep. 2011.
• [13] S. Rivera-Mancía, I. Pérez-Neri, C. Ríos, L. Tristán-López, L. Rivera-Espinosa, and S. Montes, “The transition metals copper and iron in neurodegenerative diseases,” Chem. Biol. Interact., vol. 186, no. 2, pp. 184–199, Jul. 2010.
• [14] P. A. Adlard et al., “Rapid restoration of cognition in Alzheimer’s transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta,” Neuron, vol. 59, no. 1, pp. 43–55, Jul. 2008.
• [15] H. W. Querfurth and F. M. LaFerla, “Alzheimer’s disease,” N. Engl. J. Med., vol. 362, no. 4, pp. 329–344, Jan. 2010.
• [16] M. Goedert, “Alzheimer’s and Parkinson’s diseases: The prion concept in relation to assembled Aβ, tau, and α-synuclein,” Science (80-. )., vol. 349, no. 6248, Aug. 2015.
• [17] S. Tiwari, V. Atluri, A. Kaushik, A. Yndart, and M. Nair, “Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics,” Int. J. Nanomedicine, vol. 14, pp. 5541–5554, 2019.
• [18] C. Reitz, “Alzheimer’s disease and the amyloid cascade hypothesis: a critical review,” Int. J. Alzheimers. Dis., vol. 2012, 2012.
• [19] J. C. Polanco, C. Li, L. G. Bodea, R. Martinez-Marmol, F. A. Meunier, and J. Götz, “Amyloid-β and tau complexity - towards improved biomarkers and targeted therapies,” Nat. Rev. Neurol., vol. 14, no. 1, pp. 22–40, Jan. 2018.
• [20] C. Hölscher, “Moving towards a more realistic concept of what constitutes Alzheimer’s disease,” EBioMedicine, vol. 39, p. 17, Jan. 2019.
• [21] A. C. Kim, S. Lim, and Y. K. Kim, “Metal Ion Effects on Aβ and Tau Aggregation,” Int. J. Mol. Sci. 2018, Vol. 19, Page 128, vol. 19, no. 1, p. 128, Jan. 2018.
• [22] M. Pohanka, “Oxidative stress in Alzheimer disease as a target for therapy,” Bratisl. Lek. Listy, vol. 119, no. 9, pp. 535–543, 2018.
• [23] E. Nam et al., “Regulatory Activities of Dopamine and Its Derivatives toward Metal-Free and Metal-Induced Amyloid-β Aggregation, Oxidative Stress, and Inflammation in Alzheimer’s Disease,” ACS Chem. Neurosci., vol. 9, no. 11, pp. 2655–2666, Nov. 2018.
• [24] L. Goodman, “Alzheimer’s disease: A clinico-pathologic analysis of twenty-three cases with a theory on pathogenesis,” J. Nerv. Ment. Dis., vol. 118, no. 2, pp. 97–130, 1953.
• [25] M. A. Lovell, J. D. Robertson, W. J. Teesdale, J. L. Campbell, and W. R. Markesbery, “Copper, iron and zinc in Alzheimer’s disease senile plaques,” J. Neurol. Sci., vol. 158, no. 1, pp. 47–52, Jun. 1998.
• [26] C. Ghadery et al., “R2* mapping for brain iron: associations with cognition in normal aging,” Neurobiol. Aging, vol. 36, no. 2, pp. 925–932, Feb. 2015.
• [27] B. Liu et al., “Iron promotes the toxicity of amyloid beta peptide by impeding its ordered aggregation,” J. Biol. Chem., vol. 286, no. 6, pp. 4248–4256, Feb. 2011.
• [28] T. Amit, Y. Avramovich‐Tirosh, M. B. H. Youdim, and S. Mandel, “Targeting multiple Alzheimer’s disease etiologies with multimodal neuroprotective and neurorestorative iron chelators,” FASEB J., vol. 22, no. 5, pp. 1296–1305, May 2008.
• [29] T. Uzunoglu and B. Arslan, “Possible microRNAs participating in Alzheimers pathology via signaling pathways affecting axonal transport,” J. Neurobehav. Sci., no. 0, p. 1, 2018.
• [30] B. ATASEVER ARSLAN, E. F. ARSLAN, İ. SATICI, A. YANIK, and S. KUŞOĞLU GÜLTEKİN, “Protective Effects of Folic Acid and Vitamin C Against Iron Overload at the in vitro Blood-Brain Barrier,” Int. J. Life Sci. Biotechnol., vol. 4, no. 3, pp. 353–359, Dec. 2021.
• [31] J. T. Rogers et al., “An iron-responsive element type II in the 5’-untranslated region of the Alzheimer’s amyloid precursor protein transcript,” J. Biol. Chem., vol. 277, no. 47, pp. 45518–45528, Nov. 2002.
• [32] M. T. Kabir et al., “Molecular Mechanisms of Metal Toxicity in the Pathogenesis of Alzheimer’s Disease,” Mol. Neurobiol., vol. 58, no. 1, Jan. 2021.
• [33] S. L. Sensi, A. Granzotto, M. Siotto, and R. Squitti, “Copper and Zinc Dysregulation in Alzheimer’s Disease,” Trends Pharmacol. Sci., vol. 39, no. 12, pp. 1049–1063, Dec. 2018.
• [34] M. Ventriglia, S. Bucossi, V. Panetta, and R. Squitti, “Copper in Alzheimer’s disease: a meta-analysis of serum, plasma, and cerebrospinal fluid studies,” J. Alzheimers. Dis., vol. 30, no. 4, pp. 981–984, 2012.
• [35] A. C. Kim, S. Lim, and Y. K. Kim, “Metal Ion Effects on Aβ and Tau Aggregation,” Int. J. Mol. Sci., vol. 19, no. 1, Jan. 2018.
• [36] M. Kitazawa, D. Cheng, and F. M. Laferla, “Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD,” J. Neurochem., vol. 108, no. 6, pp. 1550–1560, Mar. 2009.
• [37] K. Voss, C. Harris, M. Ralle, M. Duffy, C. Murchison, and J. F. Quinn, “Modulation of tau phosphorylation by environmental copper,” Transl. Neurodegener., vol. 3, no. 1, pp. 1–10, Nov. 2014.
• [38] E. Nam, G. Nam, and M. H. Lim, “Synaptic Copper, Amyloid-β, and Neurotransmitters in Alzheimer’s Disease,” Biochemistry, vol. 59, no. 1, pp. 15–17, Jan. 2020.
• [39] A. Takeda, “Movement of zinc and its functional significance in the brain,” Brain Res. Rev., vol. 34, no. 3, pp. 137–148, Dec. 2000.
• [40] M. A. Lovell, “A potential role for alterations of zinc and zinc transport proteins in the progression of alzheimer’s disease,” J. Alzheimer’s Dis., vol. 16, no. 3, pp. 471–483, 2009.
• [41] P. A. Adlard and A. I. Bush, “Metals and Alzheimer’s Disease: How Far Have We Come in the Clinic?,” J. Alzheimer’s Dis., vol. 62, no. 3, pp. 1369–1379, Jan. 2018.
• [42] Z. Xie, H. Wu, and J. Zhao, “Multifunctional roles of zinc in Alzheimer’s disease,” Neurotoxicology, vol. 80, pp. 112–123, Sep. 2020.
• [43] C. Haass et al., “Amyloid β-peptide is produced by cultured cells during normal metabolism,” Nat. 1992 3596393, vol. 359, no. 6393, pp. 322–325, 1992.
• [44] A. I. Bush, W. H. Pettingell, M. D. Paradis, and R. E. Tanzi, “Modulation of A beta adhesiveness and secretase site cleavage by zinc.,” J. Biol. Chem., vol. 269, no. 16, pp. 12152–12158, Apr. 1994.
• [45] A. I. Bush et al., “Rapid induction of Alzheimer Aβ amyloid formation by zinc,” Science (80-. )., vol. 265, no. 5177, pp. 1464–1467, 1994.
• [46] D. W. Vaughan and A. Peters, “The Structure of Neuritic Plaques in the Cerebral Cortex of Aged Rats,” J. Neuropathol. Exp. Neurol., vol. 40, no. 4, pp. 472–487, Jul. 1981.
• [47] M. A. Greenough et al., “Presenilins Promote the Cellular Uptake of Copper and Zinc and Maintain Copper Chaperone of SOD1-dependent Copper/Zinc Superoxide Dismutase Activity,” J. Biol. Chem., vol. 286, no. 11, pp. 9776–9786, Mar. 2011.
• [48] H. Xu et al., “Zinc affects the proteolytic stability of Apolipoprotein E in an isoform-dependent way,” Neurobiol. Dis., vol. 81, pp. 38–48, Sep. 2015.