Metals analysis in a small cohort of ALS patients originating from a restricted geographical area: preliminary data

Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disorder characterized by selective degeneration of both upper and lower motor neurons in the brain, brainstem, and spinal cord. This results in paralysis due to muscle weakness and atrophy, leading to death in 3-5 years since the first manifestations of symptoms1. Genetic and environmental factors are involved in the pathogenesis of the disease2 and metals metabolism have been linked to ALS3. Transition metal induced toxicity (including iron toxicity) has been proposed to be involved in ALS4 and higher concentrations of metals and proteins that regulate metal homeostasis have been described in ALS patients5. Thiophylic metals have been shown to be capable of displacing iron from reduced FeS proteins6, that thus may represent a yet underexplored target in this frame. We evaluated the concentration of different metals in both serum and urine by ICP-MS, in a cohort of subjects with diagnosis of ALS, originating from a restricted geographical area where the incidence of ALS is above average. Principal Component Analysis (PCA) showed higher concentrations of metals in ALS subjects, especially in urine. The only exception is for As, where lower levels have been found in ALS patients, particularly in serum samples. Artificial Neural Networks analysis was able to discriminate between subjects and controls, linking to the disease lower levels of As and higher levels of Ni. These data give an insight to the status of metals in these patients that, despite being few subjects, they share a common environmental exposure.