Heavy metals induce ALS-linked TDP-43 neuropathology

Researchers from Boston University School of Medicine (Ash et al., 2019) have reported on new data demonstrating a direct mechanistic link between exposure to heavy metals and risk for developing ALS.  These studies showed that lead (Pb) and methyl mercury (MeHg) disrupt the homeostasis of TDP-43 in neurons.  These metals also triggered the accumulation of insoluble TDP-43 in cultured cells and in the cortices of exposed mice.  These new data provide evidence for a mechanistic link between a commonly cited environmental risk factor for ALS, and molecular changes in TDP-43, the primary pathological protein accumulating in ALS.  

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