Figure 1.

The diverse major pathways by which cadmium can increase risk for neurodegenerative disease. Cadmium accumulates in the olfactory bulb following inhalation. When either inhaled or ingested, cadmium passes into the bloodstream, which can decrease the integrity of the blood–brain barrier (BBB) via weakening of tight junctions. This allows cadmium to enter into nervous system tissue. Once within the nervous tissue, cadmium can efficiently pass the cellular membrane by co-opting transporters for other divalent cations. The primary mechanisms of neurotoxicity are disruption of glycogen metabolism, changes to neurotransmitter signaling, and mitochondrial disruption leading to oxidative stress. These perturbations together increase the risk for neurodegenerative disease.