Amyotrophic Lateral Sclerosis Patients Show Higher Urinary Levels of Lead and Copper: A Pilot Case-Control Study

<b>Background/Objectives:</b> Amyotrophic Lateral Sclerosis (ALS) is the most frequent neurodegenerative disease affecting motor neurons. Sporadic ALS cases, which represent over 90% of the total, result from the interaction between genetic predisposition, aging, and environmental factors. Regarding natural environmental risk factors, the analysis of the role of exposure to heavy metals is of particular interest due to the well-known neurological effects of certain compounds. This study aims to compare the levels of heavy metals in urine samples in a cohort of patients with ALS who have not changed their living environment with the levels found in healthy controls (HCs). <b>Methods:</b> A cross-sectional case-control (14 patients with ALS vs. 28 HC) observational study was conducted in which urine samples were analyzed for five heavy metals (lead, manganese, selenium, copper, and zinc) using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). <b>Results:</b> The patients with ALS showed significantly higher urine levels of lead (<i>p</i> < 0.001) and copper (<i>p</i> = 0.007) and a subtle increase in manganese concentrations (<i>p</i> = 0.043). Urine samples reflect recent exposures, so if the source of metals was related to the residential environment (the patients in the present study had not moved), dietary habits, or certain activities or hobbies that had not changed since diagnosis, it would be representative. <b>Conclusions:</b> In this pilot study, patients with ALS presented higher urinary levels of lead, manganese, and copper. Future larger studies are needed to elucidate the precise role of these heavy metals in ALS pathogenesis.