MAMI – Medical Applications of Stable Isotopes

Elements such as Cu and Zn play critical roles in normative brain function, and thus their dysregulation is intrinsically linked to neurodegenerative disorders (Bush, 2003). When the binding environment in the brain changes in response to disease, we have shown that upon accumulation and aggregation of Aβ aggregates, this change produces a related and measurable change (excursion) in the relative abundances of naturally occurring stable isotopes, e.g., Cu and Zn, in the affected regions (by isotope fractionation). We have confirmed the hypothesis in several mouse models of Alzheimer’s disease and, more importantly, we have now confirmed it in a small group of post-mortem human brain tissues. All of this work represents the application of geochemical methods to medical science.

In this project we are continuing these studies to validate these hypotheses is whether the excursions in Cu and Zn isotopic compositions of brain tissue during AD development (confirmed in post-mortem human brain tissue; (Moynier et al., 2020) will be recapitulated by changes in Cu and Zn isotopic compositions in blood fractions. We will also extend these studies to other elements such as K or Ca.

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