Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease

Babić Leko, Mirjana; Mihelčić, Matej; Jurasović, Jasna; Nikolac Perković, Matea; Španić, Ena; Sekovanić, Ankica; Orct, Tatjana; Zubčić, Klara; Langer Horvat, Lea; Pleić, Nikolina; Kiđemet-Piskač, Spomenka; Vogrinc, Željka; Pivac, Nela; Diana, Andrea; Borovečki, Fran; Hof, Patrick R.; Šimić, Goran (2022) Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease. International Journal of Molecular Sciences, 24 (1). ISSN 1422-0067

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Abstract

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 β1- 42, 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.

Item Type:	Article
Uncontrolled Keywords:	Alzheimer’s disease; arsenic; biomarker; cadmium; calcium; cerebrospinal fluid; essential metals; heavy metals; iron; mercury; zinc
Subjects:	NATURAL SCIENCES > Biology BIOMEDICINE AND HEALTHCARE BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences BIOMEDICINE AND HEALTHCARE > Clinical Medical Sciences SOCIAL SCIENCES > Psychology INTERDISCIPLINARY AREAS OF KNOWLEDGE > Cognitive Science (Natural, Technical, Biomedical and Healthcare, Social and Humanistic Sciences)
Divisions:	Division of Molecular Medicine
Depositing User:	Kristina Ciglar
Date Deposited:	21 Apr 2026 14:32
URI:	https://fulir.irb.hr:/id/eprint/11775
DOI:	10.3390/ijms24010467

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