Abstract
This study aimed to evaluate the concentrations of copper, iron, and selenium in elderly people with Alzheimer disease (AD), comparing the same parameters in a paired group of healthy people, in order to verify if the amount of these metals may influence the cognitive impairment progression. Patients’ cognitive impairment was evaluated by Clinical Dementia Rating (CDR). The elementary quantification of erythrocytes was performed by inductively coupled plasma mass spectrometry technique. The statistical analyses were carried out by SPSS software 20.0 version, employing Shapiro-Wilk, Wilcoxon, Kruskall-Wallis, and Spearman correlation tests, considering significant results of p < 0.05. The sample was composed of 34% (n = 11) of women and 66% (n = 21) of men in each group. The AD group was characterized by a higher concentration of copper (p < 0.0001) and iron (p < 0.0001); however, there is no significant difference in selenium level. The analyses of the metal levels in different stages of AD were not significant in CDR-1, however in CDR-2 and CDR-3, elevated levels of copper and iron were observed; in CDR-3 patients, the level of selenium was lower (p < 0.008) compared to that of healthy controls. Patients with Alzheimer disease studied present increase in biometal blood levels, especially of copper and iron, and such increase can be different according to the disease stage and can cause more impairment cognitive functions in AD.
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Irvine GB, El-Agnaf OM, Shankar GM et al (2008) Protein aggregation in the brain: the molecular basis for Alzheimer’s and Parkinson’s diseases. Molecular medicine-cambridge ma then New York 14:451–464
Shahani N, Brandt R (2002) Functions and malfunctions of the tau proteins. Cell Mol Life Sci 59:1668–1680
Grant WB, Campbell A, Itzhaki RF et al (2002) The significance of environmental factors in the etiology of Alzheimer’s disease. J Alzheimers Dis 4:179–189
Viles JH (2012) Metal ions and amyloid fiber formation in neurodegenerative diseases. Copper, zinc and iron in Alzheimer’s, Parkinson’s and prion diseases. Coord Chem Rev 256:2271–2284
Candy JM, Edwardson JA, Klinowski J et al (1985) Co-localization of aluminium and silicon in senile plaques: implications for the neurochemical pathology of Alzheimer’s disease. In: Traber J, Gispen WH (eds) Senile dementia of the Alzheimer type. Advances in Applied Neurological Sciences, vol 2. Springer, Berlin, Heidelberg
Pithadia AS, Lim MH (2012) Metal-associated amyloid-β species in Alzheimer’s disease. Curr Opin Chem Biol 16:67–73
Salvador GA, Uranga RM, Giusto NM (2010) Iron and mechanisms of neurotoxicity. Int J Alzheimers Dis 2011:1–9
Walter ED, Stevens DJ, Spevacek AR et al (2009) Copper binding extrinsic to the octarepeat region in the prion protein. Current Protein and Peptide Science 10:529–535
Kozlowski H, Luczkowski M, Remelli M et al (2012) Copper, zinc and iron in neurodegenerative diseases (Alzheimer’s, Parkinson’s and prion diseases). Coord Chem Rev 256:2129–2141
Assaf S, Chung S-H (1984) Release of endogenous Zn2+ from brain tissue during activity 308:734–736
Perry G, Sayre LM, Atwood CS et al (2002) The role of iron and copper in the aetiology of neurodegenerative disorders. CNS drugs 16:339–352
Maccioni RB, Farías G, Morales I et al (2010) The revitalized tau hypothesis on Alzheimer’s disease. Arch Med Res 41:226–231
Crapper D, Krishnan S, Dalton A (1973) Brain aluminum distribution in Alzheimer’s disease and experimental neurofibrillary degeneration. Science 180:511–513
Lovell M, Robertson J, Teesdale W et al (1988) Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci 158:47–52
Nogueira C, Meotti F, Curte E et al (2003) Investigations into the potential neurotoxicity induced by diselenides in mice and rats. Toxicology 183:29–37
Santos JR, Gois AM, Mendonça DMF et al (2014) Nutritional status, oxidative stress and dementia: the role of selenium in Alzheimer’s disease. Front Aging Neurosci 6:206
Morris JC (1993) The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43:2412–2414
Moreira PI, Zhu X, Lee HG et al (2006) The (un) balance between metabolic and oxidative abnormalities and cellular compensatory responses in Alzheimer disease. Mech Ageing Dev 127:501–506
Sparks DL, Schreurs BG (2003) Trace amounts of copper in water induce β-amyloid plaques and learning deficits in a rabbit model of Alzheimer’s disease. Proc Natl Acad Sci 100:11065–11069
Morris MC, Evans DA, Tangney CC et al (2006) Dietary copper and high saturated and trans fat intakes associated with cognitive decline. Arch Neurol 63:1085–1088
Basun H, Forssell L, Wetterberg L et al (1990) Metals and trace elements in plasma and cerebrospinal fluid in normal aging and Alzheimer’s disease. Journal of neural transmission Parkinson's disease and dementia 3:231–258
Squitti R, Lupoi D, Pasqualetti P et al (2002) Elevation of serum copper levels in Alzheimer’s disease. Neurology 59:1153–1161
Squitti R, Rossini P, Cassetta E et al (2002) D-penicillamine reduces serum oxidative stress in Alzheimer’s disease patients. Eur J Clin Investig 32:51–59
Bremner I (1988) Manifestations of copper excess. Am J Clin Nutr 67:1069S–1073S
Kadiiska MB, Hanna PM, Jordan SJ et al (1993) Electron spin resonance evidence for free radical generation in copper-treated vitamin E-and selenium-deficient rats: in vivo spin-trapping investigation. Mol Pharmacol 44:222–227
Smith MA, Zhu X, Tabaton M et al (2010) Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment. J Alzheimers Dis 19:363–372
Bomboi G, Marchione F, Sepe-Monti M et al (2004) Correlation between metal ions and clinical findings in subjects affected by Alzheimer’s disease. Ann Ist Super Sanita 41:205–212
Goodman L (1953) Alzheimer’s disease: a clinico-pathologic analysis of twenty-three cases with a theory on pathogenesis. J Nerv Ment Dis 118:97–130
Huang CW, Wang SJ, Wu SJ et al (2013) Potential blood biomarker for disease severity in the Taiwanese population with Alzheimer’s disease. American journal of Alzheimer's disease and other dementias 28:75–83
Torsdottir G, Kristinsson J, Snaedal J et al (2011) Ceruloplasmin and iron proteins in the serum of patients with Alzheimer’s disease. Dementia and geriatric cognitive disorders extra 1:366–371
Vural H, Demirin H, Kara Y et al (2010) Alterations of plasma magnesium, copper, zinc, iron and selenium concentrations and some related erythrocyte antioxidant enzyme activities in patients with Alzheimer’s disease. J Trace Elem Med Biol 24:169–173
Crespo ÂC, Silva B, Marques L et al (2014) Genetic and biochemical markers in patients with Alzheimer’s disease support a concerted systemic iron homeostasis dysregulation. Neurobiol Aging 35:777–785
Bartzokis G, Tishler T (2000) MRI evaluation of basal ganglia ferritin iron and neurotoxicity in Alzheimer’s and Huntingon’s disease. Cell Mol Biol 46:821–833
Castellani RJ, Moreira PI, Liu G et al (2007) Iron: the redox-active center of oxidative stress in Alzheimer disease. Neurochem Res 32:1640–1645
Zhu X, Su B, Wang X et al (2007) Causes of oxidative stress in Alzheimer disease. Cell Mol Life Sci 64:2202–2210
Duce JA, Bush AI (2010) Biological metals and Alzheimer’s disease: implications for therapeutics and diagnostics. Prog Neurobiol 92:1–18
Zatta P, Drago D, Bolognin S et al (2009) Alzheimer’s disease, metal ions and metal homeostatic therapy. Trends Pharmacol Sci 30:346–355
Akbaraly TN, Portet F, Fustinoni S et al (2009) Leisure activities and the risk of dementia in the elderly: results from the Three-City study. Neurology 11:854–861
Cardoso BR, Ong TP, Jacob-Filho W et al (2010) Nutritional status of selenium in Alzheimer’s disease patients. Br J Nutr 103:803–806
Rivera-Mancía S, Pérez-Neri I, Ríos C et al (2010) The transition metals copper and iron in neurodegenerative diseases. Chem Biol Interact 186:184–199
Acknowledgements
The authors would like to extend their gratitude to the association of studies, research, and assistance to people with Alzheimer disease (AEPAPA), to the Araucária Foundation, and to the Higher Education Personnel Improvement Coordination (CAPES).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Vaz, F.N.C., Fermino, B.L., Haskel, M.V.L. et al. The Relationship Between Copper, Iron, and Selenium Levels and Alzheimer Disease. Biol Trace Elem Res 181, 185–191 (2018). https://doi.org/10.1007/s12011-017-1042-y
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DOI: https://doi.org/10.1007/s12011-017-1042-y