High-precision isotopic analysis of essential metals as a novel tool for unraveling their role in Alzheimer's disease and for diagnostic/prognostic purposes

This PhD research project aims to evaluate high-precision isotopic analysis of the essential metals copper (Cu), iron (Fe), zinc (Zn), calcium (Ca), magnesium (Mg) and potassium (K) as a novel means for obtaining a more profound insight into the potential role of these metals in Alzheimer’s disease and assess its use for diagnostic/prognostic purposes in this context. The A&MS group at Ghent University has previously demonstrated that some diseases (e.g., liver disease, cancer, anaemia in chronic kidney disease, diabetes type I) systematically and measurably affect the isotopic composition of specific mineral elements in body fluids and/or tissues, even when the concentration at which these elements occur is not affected. After method development, optimization and validation, multi-collector ICP-mass spectrometry (MC-ICP-MS) will be used for the isotopic analysis of Cu, Fe, Zn, Ca, Mg and K in human biofluids (serum and cerebrospinal fluid). Results for samples from patients suffering from Alzheimer’s disease, Parkinson’s disease and multiple sclerosis (cf. specificity) and from an age-matched reference population will be compared. It will be evaluated whether isotopic analysis of (one of) these elements shows promise for diagnosis or follow-up of the progression of Alzheimer’s disease. A comprehensive study relying on (three) mouse models mimicking Alzheimer’s disease will be used for unraveling the mechanisms governing isotope ratio variations.