Comparative assessment of blood Metal/metalloid levels, clinical heterogeneity, and disease severity in amyotrophic lateral sclerosis patients

Amyotrophic lateral sclerosis is an unremitting neurodegenerative (ND) disease characterized by progressive and fatal loss of motor neuron function. While underlying mechanisms for ALS susceptibility are complex, current understanding suggests that interactions between age, genetic, and environmental factors may be the key. Environmental exposure to metal/metalloids has been implicated in various ND diseases including ALS, Alzheimer's Disease (AD), and Parkinson's Disease (PD). However, most of currently available population-based ALS studies in relation to metal exposure are based on individuals from European ancestry, while East Asian populations, especially cohorts from China, are less well-characterized. This study aims to examine the association between metal/metalloid levels and ALS onset by evaluating blood cadmium (Cd), lead (Pb), Cu, Zn, calcium (Ca), magnesium (Mg), and iron (Fe) levels in controls and sporadic ALS patients from North Western China. We report that Cu and Fe levels are found at higher levels in ALS patients compared to the controls. Spinal and bulbar onset patients show significant difference in Ca levels. Moreover, Cd, Pb, Cu, and Ca levels are positively correlated with high disease severity. Results from this study may provide new insights for understanding not only the role of metal/metalloids in ALS susceptibility, but also progression and forms of onset.