Trace element species and amyotrophic lateral sclerosis with disease associated genetic mutations

Introduction: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with mostly unknown eti-ology. Certain genetic mutations are associated with the disease; however, the role of environmental factors, such as exposure to metals and organic pollutants is also widely discussed in the literature. ALS, as other neurodegenerative disorders, is related to the brain oxidative stress, so the disturbance of redox homeostasis may be anticipated for such elements as selenium (Se), copper (Cu), iron (Fe), and manganese (Mn). Aim: The aim of the study was to evaluate a possible alteration of trace element (Se, Cu, Mn, and Fe) homeostasis in the ALS patients with disease associated gene mutations. Methods: We analyzed cerebrospinal fluid (CSF) samples from 9 patients with ALS-associated muta-tions (C9ORF72, SOD1, FUS, TARDBP, ATXN2, and TUBA4A) and 42 age- and gender-matched controls. Advanced speciation techniques were used to quantify redox forms of Cu (I/II), Mn (II/III), and Fe (II/III) and Se species (selenoprotein P, glutathione peroxidase, thioredoxin reductase, selenite, selenate, and human serum bound-Se). For the separation of Se species strong anion exchange chromatography (SAX) was used, whereas Cu, Mn, and Fe redox forms were separated by strong cation exchange (SCX). For the species detection, inductively coupled plasma sector field mass spectrometry (ICP-sf-MS), op-erated at high resolution for Se or medium resolution for Cu, Fe, and Mn was employed. Standard compounds and spikings were used for peak assignment. External calibration vs. matching to the total content of the elements, measured by inductively coupled plasma dynamic reaction cell mass spec-trometry, was used for species quantification. Results: The analytical schemes of species quantification, using SAX-ICP-sf-MS [1] and SCX-ICP-sf-MS [2], have been optimized. The difference in Cu(II) and some Se species were found to be altered in the CSF of the ALS patients with disease-associated mutations. Also, since multi-element speciation had been performed for the same set of CSF samples, some inter-element correlations were observed (be-tween Fe and Se species, Mn and Fe, Mn and Cu). Conclusion: Despite the limited sample size, we could presume a distortion in trace element metabo-lism, reflected the altered speciation of Cu and Se in the CSF. However, more insight is required to understand if these findings are an innocent bystander to the pathological changes in the ALS brain or has its own relevant role in the etiopathogenesis of the disease.