Unraveling the natural isotopic fractionation of Fe accompanying different homeostatic processes for understanding the effect of impaired Fe regulation on its isotopic composition in biological fluids.

Understanding the source bio-mechanisms of Fe isotopic fractionation in the human body is crucial knowledge for developing diagnostic tools of one's Fe status. Now, quantification of serum ferritin levels is relied on, but results may be often misleading as they can be affected by inflammation, infection and liver disorders. Isotopic analysis of blood/serum Fe is gaining potential as a robust and reliable indicator of the Fe status. However, the Fe metabolic processes that lead to isotopic fractionation are not fully understood. In this project, different cell lines will be used for the in vitro study of Fe isotopic fractionation accompanying Fe fluxes at the most relevant metabolic points. The correlation of several medical parameters with the Fe isotopic composition of serum samples of hemochromatosis type IV patients will be evaluated to validate the in vitro findings. Brain Fe homeostasis will be tackled in parallel to evaluate the oxidative role of metals in the brain. Paired serum/CSF samples from healthy and Alzheimer´s disease patients will be available with the aim of finding a suitable biomarker for an early diagnosis, when therapeutic treatments are more relevant. Methods for separating Fe-bound proteins and non-bound Fe in such samples will be optimized for next isotopic analysis of the fractions to evaluate the contribution of the predominant species to the total isotopic composition and the potential of species-specific isotopic analysis as a diagnostic tool.