Elevated Blood and Urine Metal Concentrations to Heighten ALS Risk
Occupations with high metal exposure were also associated with an elevated risk for ALS.
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A recent study, from the University of Michigan, discovered that elevated levels of metals in the blood and urine may raise the risk of being diagnosed with (and dying from) amyotrophic lateral sclerosis (ALS). The study was published in the Journal of Neurology Neuroscience & Psychiatry.
ALS is a rare but fatal disease
ALS is a motor neuron disease that affects the neurons in the brain and spinal cord responsible for controlling voluntary muscle movement and breathing. As the condition progresses, motor neurons degenerate and die, resulting in the loss of signals sent to the muscles. This leads to muscle weakness and atrophy, contributing to declines in function. Symptoms progressively decline, eventually causing respiratory failure when patients can no longer breathe on their own. Most individuals with ALS die within three to five years from when symptoms appear.
Although it is not yet known what causes ALS, researchers believe it may be a combination of both genetic and environmental factors. Previous studies have highlighted exposure to pesticides and metals may increase the risk of developing the disease. The team from Michigan Medicine also conducted a research study in 2019 that demonstrated people with ALS reported higher occupational exposure to metals prior to diagnosis.
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Subscribe for FREE“Several epidemiologic studies have linked metal exposure to ALS risk. Nonetheless, it remains critical for us to understand how these metal mixtures associate with ALS risk and survival and to identify who is at greatest risk of exposure or who is most susceptible to the exposure,” said corresponding author Dr. Stephen A Goutman, an associate professor in the department of neurology at Michigan Medicine.
Presence of metals in plasma and urine increases disease risk
Goutman and his team assessed metal levels in plasma and urine samples from 454 participants with ALS and 294 controls using inductively coupled plasma mass spectrometry.
Elevated levels of individual metals, such as copper, selenium and zinc were significantly linked with an increased risk of ALS and earlier death.
These results were then used to develop environmental ALS risk scores (similar to polygenic risk scores) which indicated that the presence of metal mixtures in plasma and urine is associated with a threefold increase in disease risk. ALS polygenic risk scores were also used to assess the potential of underlying genetic factors affecting the results.
Polygenic risk scores
Polygenic risk scores refer to a value that represents the total number of genetic variants an individual has, allowing prediction of their risk in developing a particular disease.
“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 co-author Dr. Kelly Bakulski, an associate professor of epidemiology at the University of Michigan.
Preventing ALS
Although there is still a strong association between the impact of genetics on ALS risk, the research underscores the importance of considering metal exposure on disease risk and progression.
“The relationships between genes and the environment on disease risk are complex. Future insights into other genetic factors or pathways that may be involved in ALS risk and metabolism of metals could enhance our understanding,” said Bakulski.
“Our future research will further focus on what exposures have the strongest associations and implications on the disease,” said first author Dr. Dae Gyu Jang, a postdoctoral fellow in the Department of Neurology at the University of Michigan .
“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 Goutman.
Reference: Jang DG, Dou JF, Koubek EJ, et al. Multiple metal exposures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study. J Neurol Neurosurg Psychiatry. 2024. doi: 10.1136/jnnp-2024-333978
This article is a rework of a press release issued by the University of Michigan. Material has been edited for length and content.
