Previous studies have identified molecular profiles and risk factors that contribute to Alzheimer’s disease (AD) and AD-related dementias, including genetics, traumatic brain injury, cerebrovascular pathology, and neuroinflammation. These risk factors are modulated by a high-fat diet, sedentary lifestyle, and cumulative lifetime exposure to environmental toxicants (“exposome”), including heavy metals. This study focuses on exposure to lead (Pb), cadmium (Cd), and arsenic (As), listed by the World Health Organization among the “Top 10” chemical toxicants of public health concern.

The initial study utilized mice of both sexes to establish levels of metal/metalloid retention in the brain, blood, and kidneys after 30-day exposure to Pb (200 ppm), Cd (5 and 50 ppm), As (20 ppm), control (no added metal) in drinking water. No group differences were noted in daily weight or water intake. Brain, kidneys, and blood were collected, frozen using liquid nitrogen, and stored at -80C until tissue processing. Tissue concentrations of exogenously administered metal/metalloid toxicants (Pb, Cd, As) and endogenous biometals (Zn, Cu, Fe) were evaluated by inductively coupled plasma mass spectrometry (ICP-MS) solution analysis and LA-ICP-MS.

ICP-MS results showed robust Pb, Cd, and As uptake in mouse brain, kidneys, and blood after 30-day exposure to epidemiologically relevant levels of each metal/metalloid in drinking water. We also demonstrated a strong correlation between brain and blood levels of As, Cd, and Pb. LA-ICP-MS mapping showed that neurotoxicants have non-homogeneous element-specific accumulation in different brain regions and subregions, including the hippocampus and cortex. Additionally, we observed a significant increase in copper levels in the kidney of a mouse exposed to arsenic. This change in copper homeostasis in the kidney shows a possible interaction with arsenic exposure.