Metal ratios as possible biomarkers for amyotrophic lateral sclerosis

Abstract

Background and objectives: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown aetiology. Metals have been suspected to contribute to ALS pathogenesis since mid-19th century, yet studies on measured metal concentrations in ALS patients have often yielded conflicting results, with large individual variation in measured values. Calculating metal concentration ratios can unveil possible synergistic effects of neurotoxic metals in ALS pathogenesis. The aim of this study was to investigate if ratios of different metal concentrations in cerebrospinal fluid (CSF) and blood plasma, respectively, differ between ALS patients and healthy controls.

Methods: Cerebrospinal fluid and blood plasma were collected from 17 ALS patients and 10 controls. Samples were analysed for 22 metals by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS), and all possible 231 metal ratios calculated in each body fluid.

Results: Fifty-three metal ratios were significantly elevated in ALS cases as compared to controls (p < 0.05); five in blood plasma, and 48 in CSF. The finding of fewer elevated ratios in blood plasma may indicate specific transport of metals into the central nervous system. The elevated metal ratios in CSF include Cd/Se (p = 0.031), and 16 ratios with magnesium, such as Mn/Mg (p = 0.005) and Al/Mg (p = 0.014).

Conclusion: Metal ratios may be used as biomarkers in ALS diagnosis and as guidelines for preventive measures.

Keywords: Metal exposure; Neurodegeneration; Neuroprotection; Neurotoxicity; Ratio.