Distribution and Interaction of Lead (Pb),  Mercury (Hg), Selenium (Se), and Other Metals in Brain Tissue Using  Synchrotron Micro-X-ray Fluorescence

Alzheimer’s disease (AD) is a progressive neurodegenerative disease affecting more than 6 million individuals in the United States and more than 50 million worldwide. Currently, there exists no cure for AD and there are very few treatments to limit disease progression. Understanding the mechanisms through which AD develops and the risk factors associated with disease onset and progression is imperative in diagnosis and treatment of AD. Metal dysregulation has been implicated in disease pathogenesis through a number of mechanisms. Toxic heavy metals, such as lead (Pb) and mercury (Hg) are known to have deleterious effects on the central nervous system (CNS) and have been shown to increase AD pathology in animal models. However, there are significant knowledge gaps on how these metals deposit in human and animal brains at the microscopic scale, how they interact with essential metals in brain, and the relation of heavy metal exposure and AD. In this project, we aimed to investigate the distribution of heavy metals and their interactions with essential elements in transgenic mouse and human brain tissue models. We report, for the first time, Pb distribution and its co-deposition with Se in mouse brains following subchronic Pb exposure, Hg distribution and its co-deposition with Se in post-mortem AD and no cognitive impairment (NCI) brains, and the association of Pb, Hg, and other metals in these brains. All the data were obtained using synchrotron x-ray fluorescence (XRF), a powerful technique that allows for localization and quantification of multiple biological elements, as well as heavy metals, with a high spatial resolution and low detection limit. The work will shed light on the role essential metals, especially Se, play in neurotoxicity of Pb and Hg, and pave the way for potential future directions on heavy metal exposure and neurodegeneration.