Elevated selenium and lead concentrations in amyotrophic lateral sclerosis cerebrospinal fluid provide clues to ALS pathogenesis

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration and muscle atrophy, ultimately leading to death through respiratory failure. Environmental factors, including metal exposure, seem to contribute to ALS pathogenesis. Elevated concentrations of metals such as Pb, Se, and Cd have been detected in ALS cerebrospinal fluid (CSF) and blood from ALS patients, providing clues to possible pathogenesis. Here we conducted a detailed analysis of CSF and blood plasma samples collected by ultraclean techniques from seven ALS patients and seven healthy controls. Inductively coupled plasma mass spectrometry (ICP-MS) was used for metal measurements. Significantly higher concentrations of ²⁰⁸ Pb and ⁷⁸ Se (p < 0.01), and lower concentrations of ⁷⁵ As and ⁵⁵ Mn (p < 0.05), were found in ALS CSF but not in ALS blood plasma. Additionally, ALS patients displayed increased concentrations of ⁶⁰ Ni in blood plasma relative to controls (p < 0.05). Elevated ²⁰⁸ Pb/ ²⁰⁶ Pb and ²⁰⁶ Pb/ ²⁰⁷ Pb ratios were observed in ALS CSF, possibly tracing sources of lead exposure. Samples were also analyzed using size-exclusion chromatography coupled with ICP-MS to monitor the distribution of metals between different protein carriers. The combined findings support the hypothesis that metal exposure contributes to the pathogenesis of ALS.