Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease
Various metals have been associated with the pathogenesis of Alzheimer’s disease (AD), principally heavy metals that are environmental pollutants (such as As, Cd, Hg, and Pb) and essential metals whose homeostasis is disturbed in AD (such as Cu, Fe, and Zn). Although there is evidence of the involve...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/1/467 |
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| author | Mirjana Babić Leko Matej Mihelčić Jasna Jurasović Matea Nikolac Perković Ena Španić Ankica Sekovanić Tatjana Orct Klara Zubčić Lea Langer Horvat Nikolina Pleić Spomenka Kiđemet-Piskač Željka Vogrinc Nela Pivac Andrea Diana Fran Borovečki Patrick R. Hof Goran Šimić |
| author_facet | Mirjana Babić Leko Matej Mihelčić Jasna Jurasović Matea Nikolac Perković Ena Španić Ankica Sekovanić Tatjana Orct Klara Zubčić Lea Langer Horvat Nikolina Pleić Spomenka Kiđemet-Piskač Željka Vogrinc Nela Pivac Andrea Diana Fran Borovečki Patrick R. Hof Goran Šimić |
| author_sort | Mirjana Babić Leko |
| collection | DOAJ |
| description | Various metals have been associated with the pathogenesis of Alzheimer’s disease (AD), principally heavy metals that are environmental pollutants (such as As, Cd, Hg, and Pb) and essential metals whose homeostasis is disturbed in AD (such as Cu, Fe, and Zn). Although there is evidence of the involvement of these metals in AD, further research is needed on their mechanisms of toxicity. To further assess the involvement of heavy and essential metals in AD pathogenesis, we compared cerebrospinal fluid (CSF) AD biomarkers to macro- and microelements measured in CSF and plasma. We tested if macro- and microelements’ concentrations (heavy metals (As, Cd, Hg, Ni, Pb, and Tl), essential metals (Na, Mg, K, Ca, Fe, Co, Mn, Cu, Zn, and Mo), essential non-metals (B, P, S, and Se), and other non-essential metals (Al, Ba, Li, and Sr)) are associated with CSF AD biomarkers that reflect pathological changes in the AD brain (amyloid β<sub>1–42</sub>, total tau, phosphorylated tau isoforms, NFL, S100B, VILIP-1, YKL-40, PAPP-A, and albumin). We used inductively coupled plasma mass spectroscopy (ICP-MS) to determine macro- and microelements in CSF and plasma, and enzyme-linked immunosorbent assays (ELISA) to determine protein biomarkers of AD in CSF. This study included 193 participants (124 with AD, 50 with mild cognitive impairment, and 19 healthy controls). Simple correlation, as well as machine learning algorithms (redescription mining and principal component analysis (PCA)), demonstrated that levels of heavy metals (As, Cd, Hg, Ni, Pb, and Tl), essential metals (Ca, Co, Cu, Fe, Mg, Mn, Mo, Na, K, and Zn), and essential non-metals (P, S, and Se) are positively associated with CSF phosphorylated tau isoforms, VILIP-1, S100B, NFL, and YKL-40 in AD. |
| first_indexed | 2024-03-11T09:58:57Z |
| format | Article |
| id | doaj.art-75bd3cfccd934e9f818cb3dc968eeccd |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:58:57Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-75bd3cfccd934e9f818cb3dc968eeccd2023-11-16T15:33:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0124146710.3390/ijms24010467Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s DiseaseMirjana Babić Leko0Matej Mihelčić1Jasna Jurasović2Matea Nikolac Perković3Ena Španić4Ankica Sekovanić5Tatjana Orct6Klara Zubčić7Lea Langer Horvat8Nikolina Pleić9Spomenka Kiđemet-Piskač10Željka Vogrinc11Nela Pivac12Andrea Diana13Fran Borovečki14Patrick R. Hof15Goran Šimić16Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaDepartment of Mathematics, University of Zagreb Faculty of Science, 10000 Zagreb, CroatiaAnalytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, 10000 Zagreb, CroatiaRuđer Bošković Institute, Division of Molecular Medicine, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaAnalytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, 10000 Zagreb, CroatiaAnalytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaDepartment of Medical Biology, University of Split School of Medicine, 21000 Split, CroatiaDepartment of Neurology, General Hospital Varaždin, 42000 Varaždin, CroatiaLaboratory for Neurobiochemistry, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, 10000 Zagreb, CroatiaRuđer Bošković Institute, Division of Molecular Medicine, 10000 Zagreb, CroatiaLaboratory of Neurogenesis and Neuropoiesis, Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042 Cagliari, ItalyDepartment for Functional Genomics, Center for Translational and Clinical Research, University of Zagreb Medical School, University Hospital Center Zagreb, 10000 Zagreb, CroatiaNash Family Department of Neuroscience, Friedman Brain Institute, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaVarious metals have been associated with the pathogenesis of Alzheimer’s disease (AD), principally heavy metals that are environmental pollutants (such as As, Cd, Hg, and Pb) and essential metals whose homeostasis is disturbed in AD (such as Cu, Fe, and Zn). Although there is evidence of the involvement of these metals in AD, further research is needed on their mechanisms of toxicity. To further assess the involvement of heavy and essential metals in AD pathogenesis, we compared cerebrospinal fluid (CSF) AD biomarkers to macro- and microelements measured in CSF and plasma. We tested if macro- and microelements’ concentrations (heavy metals (As, Cd, Hg, Ni, Pb, and Tl), essential metals (Na, Mg, K, Ca, Fe, Co, Mn, Cu, Zn, and Mo), essential non-metals (B, P, S, and Se), and other non-essential metals (Al, Ba, Li, and Sr)) are associated with CSF AD biomarkers that reflect pathological changes in the AD brain (amyloid β<sub>1–42</sub>, total tau, phosphorylated tau isoforms, NFL, S100B, VILIP-1, YKL-40, PAPP-A, and albumin). We used inductively coupled plasma mass spectroscopy (ICP-MS) to determine macro- and microelements in CSF and plasma, and enzyme-linked immunosorbent assays (ELISA) to determine protein biomarkers of AD in CSF. This study included 193 participants (124 with AD, 50 with mild cognitive impairment, and 19 healthy controls). Simple correlation, as well as machine learning algorithms (redescription mining and principal component analysis (PCA)), demonstrated that levels of heavy metals (As, Cd, Hg, Ni, Pb, and Tl), essential metals (Ca, Co, Cu, Fe, Mg, Mn, Mo, Na, K, and Zn), and essential non-metals (P, S, and Se) are positively associated with CSF phosphorylated tau isoforms, VILIP-1, S100B, NFL, and YKL-40 in AD.https://www.mdpi.com/1422-0067/24/1/467Alzheimer’s diseaseheavy metalsessential metalscerebrospinal fluidbiomarkerarsenic |
| spellingShingle | Mirjana Babić Leko Matej Mihelčić Jasna Jurasović Matea Nikolac Perković Ena Španić Ankica Sekovanić Tatjana Orct Klara Zubčić Lea Langer Horvat Nikolina Pleić Spomenka Kiđemet-Piskač Željka Vogrinc Nela Pivac Andrea Diana Fran Borovečki Patrick R. Hof Goran Šimić Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease International Journal of Molecular Sciences Alzheimer’s disease heavy metals essential metals cerebrospinal fluid biomarker arsenic |
| title | Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease |
| title_full | Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease |
| title_fullStr | Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease |
| title_full_unstemmed | Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease |
| title_short | Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease |
| title_sort | heavy metals and essential metals are associated with cerebrospinal fluid biomarkers of alzheimer s disease |
| topic | Alzheimer’s disease heavy metals essential metals cerebrospinal fluid biomarker arsenic |
| url | https://www.mdpi.com/1422-0067/24/1/467 |
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