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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\u2019 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 \u03b21\u201342, 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.<\/jats:p>","DOI":"10.3390\/ijms24010467","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T05:42:48Z","timestamp":1672206168000},"page":"467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4223-4190","authenticated-orcid":false,"given":"Mirjana","family":"Babi\u0107 Leko","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"},{"name":"Department of Medical Biology, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matej","family":"Mihel\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of Zagreb Faculty of Science, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3183-7327","authenticated-orcid":false,"given":"Jasna","family":"Jurasovi\u0107","sequence":"additional","affiliation":[{"name":"Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3113-0778","authenticated-orcid":false,"given":"Matea","family":"Nikolac Perkovi\u0107","sequence":"additional","affiliation":[{"name":"Ru\u0111er Bo\u0161kovi\u0107 Institute, Division of Molecular Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ena","family":"\u0160pani\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6855-1018","authenticated-orcid":false,"given":"Ankica","family":"Sekovani\u0107","sequence":"additional","affiliation":[{"name":"Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9301-4035","authenticated-orcid":false,"given":"Tatjana","family":"Orct","sequence":"additional","affiliation":[{"name":"Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Zub\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Langer Horvat","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5672-871X","authenticated-orcid":false,"given":"Nikolina","family":"Plei\u0107","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spomenka","family":"Ki\u0111emet-Piska\u010d","sequence":"additional","affiliation":[{"name":"Department of Neurology, General Hospital Vara\u017edin, 42000 Vara\u017edin, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017deljka","family":"Vogrinc","sequence":"additional","affiliation":[{"name":"Laboratory for Neurobiochemistry, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nela","family":"Pivac","sequence":"additional","affiliation":[{"name":"Ru\u0111er 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