Researchers from the University of Michigan, reporting in the journal Neurology, Neurosurgery & Psychiatry, say that people with high levels of individual metals detected in the blood and urine are more likely to be diagnosed and die from amyotrophic lateral sclerosis (ALS). Specifically, elevated levels of individual metals, including copper, selenium, and zinc were significantly associated with ALS risk and survival.
“Strengthening our understanding of the importance of exposure to metals as a risk factor for ALS is essential for future targeted prevention of the disease and improved therapeutic strategies,” said senior author Stephen Goutman, MD, director of the Pranger ALS Clinic and associate director of the ALS Center of Excellence at University of Michigan.
For their research, the University of Michigan team examined metal levels in blood and plasma samples using mass spectrometry in more than 450 people with ALS and another 300 people without the neurodegenerative disease. Using their findings, the team then sought to create an ALS risk score, similar to polygenic risk scores (PRS) to attempt to quantify the risk of people for ALS development based on the metals found in a person’s blood and urine.
From this scoring model, Goutman and colleagues showed that their environmental risk scores indicated metals in the blood and urine are linked to a nearly three times greater risk of developing ALS. The inclusion of their ALS polygenic risk scores to assess any potential genetic moderating effect showed these did not alter the risk associated with metal exposure to disease risk or survival.
“While several studies suggest that environmental factors like metals interact with genetic variants to influence the onset, progression and severity of ALS, our study found that accounting for ALS polygenic risk scores did not influence the relationship between metal exposure and ALS,” said Kelly Bakulski, PhD, associate professor of epidemiology at the University of Michigan School of Public Health and study co-author.
Nevertheless, Bakulski pointed out, the relationship between environmental exposure and genetic factors on increasing or decreasing disease risk are complex and future findings that better elucidate the pathways of ALS and metabolism of metals could provide further insights.
Not surprisingly, the researchers found that people working in occupations with higher likelihood of environmental exposure to metals, also had high levels of metals in their blood and urine, which confirmed the investigators’ prior research showing that people with ALS reported higher exposure to metals in the workplace prior to their ALS diagnosis.
“These findings emphasize the necessity of accounting for occupational and environmental factors when evaluating a person’s overall exposure risk,” said first author Dae-Gyu Jang, PhD, postdoctoral fellow in the U-M Health Department of Neurology.
Continuing their research, the team will look for which exposures have the highest associations with metal levels and their potential implications with disease development, Goutman noted.
