The association of exposure to lead, mercury, and selenium and the development of amyotrophic lateral sclerosis and the epigenetic implications.

Metal exposures are an intriguing potential culprit in the cause of sporadic amyotrophic lateral sclerosis (ALS). For one, there are numerous case reports linking different metals to an ALS phenotype. Furthermore, some investigators have demonstrated higher levels of certain metals in the blood, bone, cerebrospinal fluid, urine, or spinal cords of patients with ALS compared to controls. There are also many case-control studies looking at the possible association of certain metals with the development of ALS. We have reviewed the relevant literature regarding metal exposures and the risk of developing ALS. We found that many different metals have been implicated as having a role in ALS, but there is more literature investigating the role of lead than any other metal. Despite many studies, the role, if any, of this metal in the pathogenesis of ALS remains unclear. Similarly, other metals either have inconclusive, conflicting, or insufficient results in order to make a definitive conclusion. One explanation for these findings is that metal exposures alone are insufficient for the development of ALS. Perhaps an interaction between the metal exposure and an individual's genetic makeup is required to produce epigenetic changes that ultimately lead to ALS.