A perspective on persistent toxicants in veterans and amyotrophic lateral sclerosis: identifying exposures determining higher ALS risk

Diane B. Re, Beizhan Yan, Lilian Calderón-Garcidueñas, Angeline S. Andrew, Maeve Tischbein, Elijah W. Stommel

Research output: Contribution to journalReview articlepeer-review

Abstract

Multiple studies indicate that United States veterans have an increased risk of developing amyotrophic lateral sclerosis (ALS) compared to civilians. However, the responsible etiological factors are unknown. In the general population, specific occupational (e.g. truck drivers, airline pilots) and environmental exposures (e.g. metals, pesticides) are associated with an increased ALS risk. As such, the increased prevalence of ALS in veterans strongly suggests that there are exposures experienced by military personnel that are disproportionate to civilians. During service, veterans may encounter numerous neurotoxic exposures (e.g. burn pits, engine exhaust, firing ranges). So far, however, there is a paucity of studies investigating environmental factors contributing to ALS in veterans and even fewer assessing their exposure using biomarkers. Herein, we discuss ALS pathogenesis in relation to a series of persistent neurotoxicants (often emitted as mixtures) including: chemical elements, nanoparticles and lipophilic toxicants such as dioxins, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. We propose these toxicants should be directly measured in veteran central nervous system tissue, where they may have accumulated for decades. Specific toxicants (or mixtures thereof) may accelerate ALS development following a multistep hypothesis or act synergistically with other service-linked exposures (e.g. head trauma/concussions). Such possibilities could explain the lower age of onset observed in veterans compared to civilians. Identifying high-risk exposures within vulnerable populations is key to understanding ALS etiopathogenesis and is urgently needed to act upon modifiable risk factors for military personnel who deserve enhanced protection during their years of service, not only for their short-term, but also long-term health.

Original languageEnglish
Pages (from-to)2359-2377
Number of pages19
JournalJournal of Neurology
Volume269
Issue number5
DOIs
StatePublished - May 2022

Keywords

  • Amyotrophic lateral sclerosis
  • Etiology
  • Exposure
  • Neurotoxicant
  • Persistent
  • Veterans

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