Elucidating the mechanisms of cadmium neurotoxicity after low-level exposures

The identification of environmental risk factors suggests that Alzheimer's disease (AD) is preventable. Among the environmental risk factors, the neurotoxic metal cadmium is of great concern because exposure is widespread. The mechanisms of cadmium-induced neurotoxicity are largely unknown, hampering the development of effective prevention strategies. Using synchrotron imaging, we will show that cadmium accumulates in critical regions of neurons from the hippocampus, a brain region that is affected early and severely in AD. Hippocampal neurons are very rich in Zn, a physiological metal that is readily substituted by Cd upon exposure. We expect to show that Cd is present in the Zn-rich post-synaptic density, mitochondria and along dendrites disrupting synaptic structure and function. These results will serve as a basis for prevention strategies using Zn supplementation in at-risk individuals.