Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer's Disease.
Mirjana Babić LekoMatej MihelčićJasna JurasovićMatea Nikolac PerkovicEna ŠpanićAnkica SekovanićTatjana OrctKlara ZubčićLea Langer HorvatNikolina PleićSpomenka Kiđemet-PiskačŽeljka VogrincNela PivacAndrea DianaFran BorovečkiPatrick R HofGoran ŠimićPublished in: International journal of molecular sciences (2022)
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 1-42 , 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.
Keyphrases
- heavy metals
- health risk assessment
- health risk
- cerebrospinal fluid
- risk assessment
- human health
- machine learning
- mild cognitive impairment
- metal organic framework
- aqueous solution
- sewage sludge
- cognitive decline
- multiple sclerosis
- oxidative stress
- high resolution
- artificial intelligence
- mass spectrometry
- small molecule
- high throughput
- room temperature
- white matter
- simultaneous determination