Characterization of cadmium-induced protein aggregation mechanisms associated to Alzheimer's disease

Recent studies have implicated cadmium (Cd), a neurotoxic metal, in the development of Alzheimer’s disease (AD). Cd accumulates in the hippocampus, a brain region that is affected early and severely in AD. As Cd can easily compete with zinc (Zn)-binding sites in cells, we hypothesise that Cd could accumulate in Zn-rich mossy fibres (MF), where early tau pathology emerges. The Tau protein has three Zn-binding sites and Cd may substitute for Zn, thereby promoting Tau aggregation. Using mouse organotypic hippocampal slice cultures (OHSCs) and nanoXRF imaging, we aim to demonstrate the accumulation of Cd in MF and its correlation with Tau aggregation by comparing SXRF elemental maps with OHSCs adjacent sections labelled with a phospho-Tau antibody.