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The Association of Essential Metals with APOE Genotype in Alzheimer's Disease.
J Alzheimers Dis. 2021; 82(2):661-672.JA

Abstract

BACKGROUND

The major confirmed genetic risk factor for late-onset, sporadic Alzheimer's disease (AD) is variant ɛ4 of apolipoprotein E gene (APOE). It is proposed that ApoE, a protein involved in transport of cholesterol to neurons can cause neurodegeneration in AD through interaction with metals. Previous studies mostly associated copper, iron, zinc, and calcium with ApoE4-mediated toxicity.

OBJECTIVE

To test the association of essential metals with APOE genotype.

METHODS

We compared plasma and cerebrospinal fluid (CSF) levels of copper, zinc, iron, sodium, magnesium, calcium, cobalt, molybdenum, manganese, boron, and chromium, and CSF ferritin levels among AD, mild cognitive impairment (MCI) patients, and healthy controls (HC) with different APOE genotype.

RESULTS

Sodium, copper, and magnesium levels were increased in carriers of ɛ4 allele. Additionally, the increase in sodium, calcium and cobalt plasma levels was observed in carriers of ɛ4/ɛx genotype. The decrease in boron plasma levels was observed in carriers of ɛ4 allele and ɛ4/ɛ4 genotype. Additionally, CSF zinc levels as well as plasma sodium levels were increased in AD patients compared to HC.

CONCLUSION

These results indicate that the molecular underpinnings of association of essential metals and metalloids with APOE should be further tested and clarified in vivo and in vitro.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Babić Leko M
Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
Jurasović J
Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
Nikolac Perković M
Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia.
Španić E
Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
Sekovanić A
Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
Orct T
Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
Lukinović Škudar V
Department of Physiology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
Bačić Baronica K
University Department of Neurology, Clinical Hospital "Sveti Duh", Zagreb, Croatia and Neurology Clinic, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
Kiđemet-Piskač S
Department of Neurology, General Hospital Varaždin, Varaždin, Croatia.
Vogrinc Ž
Laboratory for Neurobiochemistry, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia.
Pivac N
Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia.
Borovečki F
Department for Functional Genomics, Center for Translational and Clinical Research, University of Zagreb Medical School, University Hospital Center Zagreb, Zagreb, Croatia.
Hof PR
Nash Family Department of Neuroscience, Friedman Brain Institute, and Ronald M. Loeb Center for Alzheimer's disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Šimić G
Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.

MeSH

AgedAlzheimer DiseaseApolipoprotein E4Apolipoproteins EBiological TransportCholesterolCognitive DysfunctionCorrelation of DataFemaleFerritinsGenotypeHumansMaleMetalloidsMetalsSodiumZinc

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34057084

Citation

Babić Leko, Mirjana, et al. "The Association of Essential Metals With APOE Genotype in Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 82, no. 2, 2021, pp. 661-672.
Babić Leko M, Jurasović J, Nikolac Perković M, et al. The Association of Essential Metals with APOE Genotype in Alzheimer's Disease. J Alzheimers Dis. 2021;82(2):661-672.
Babić Leko, M., Jurasović, J., Nikolac Perković, M., Španić, E., Sekovanić, A., Orct, T., Lukinović Škudar, V., Bačić Baronica, K., Kiđemet-Piskač, S., Vogrinc, Ž., Pivac, N., Borovečki, F., Hof, P. R., & Šimić, G. (2021). The Association of Essential Metals with APOE Genotype in Alzheimer's Disease. Journal of Alzheimer's Disease : JAD, 82(2), 661-672. https://doi.org/10.3233/JAD-210158
Babić Leko M, et al. The Association of Essential Metals With APOE Genotype in Alzheimer's Disease. J Alzheimers Dis. 2021;82(2):661-672. PubMed PMID: 34057084.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Association of Essential Metals with APOE Genotype in Alzheimer's Disease. AU - Babić Leko,Mirjana, AU - Jurasović,Jasna, AU - Nikolac Perković,Matea, AU - Španić,Ena, AU - Sekovanić,Ankica, AU - Orct,Tatjana, AU - Lukinović Škudar,Vesna, AU - Bačić Baronica,Koraljka, AU - Kiđemet-Piskač,Spomenka, AU - Vogrinc,Željka, AU - Pivac,Nela, AU - Borovečki,Fran, AU - Hof,Patrick R, AU - Šimić,Goran, PY - 2021/6/1/pubmed PY - 2021/9/21/medline PY - 2021/5/31/entrez KW - Alzheimer’s disease KW - apolipoprotein E KW - copper KW - metals KW - mild cognitive impairment KW - zinc SP - 661 EP - 672 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 82 IS - 2 N2 - BACKGROUND: The major confirmed genetic risk factor for late-onset, sporadic Alzheimer's disease (AD) is variant ɛ4 of apolipoprotein E gene (APOE). It is proposed that ApoE, a protein involved in transport of cholesterol to neurons can cause neurodegeneration in AD through interaction with metals. Previous studies mostly associated copper, iron, zinc, and calcium with ApoE4-mediated toxicity. OBJECTIVE: To test the association of essential metals with APOE genotype. METHODS: We compared plasma and cerebrospinal fluid (CSF) levels of copper, zinc, iron, sodium, magnesium, calcium, cobalt, molybdenum, manganese, boron, and chromium, and CSF ferritin levels among AD, mild cognitive impairment (MCI) patients, and healthy controls (HC) with different APOE genotype. RESULTS: Sodium, copper, and magnesium levels were increased in carriers of ɛ4 allele. Additionally, the increase in sodium, calcium and cobalt plasma levels was observed in carriers of ɛ4/ɛx genotype. The decrease in boron plasma levels was observed in carriers of ɛ4 allele and ɛ4/ɛ4 genotype. Additionally, CSF zinc levels as well as plasma sodium levels were increased in AD patients compared to HC. CONCLUSION: These results indicate that the molecular underpinnings of association of essential metals and metalloids with APOE should be further tested and clarified in vivo and in vitro. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/34057084/The_Association_of_Essential_Metals_with_APOE_Genotype_in_Alzheimer's_Disease_ DB - PRIME DP - Unbound Medicine ER -