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Stable potassium isotope ratios in human blood serum towards biomarker development in Alzheimer's disease.

Brandon MahanYan HuEsther LahoudMark NestmeyerAlex McCoy-WestGrace ManestarChristopher FowlerAshley I BushFrederic Moynier
Published in: Metallomics : integrated biometal science (2024)
The Alzheimer's disease (AD) affected brain purges K with concurrently increasing serum K, suggesting brain-blood K transferal. Here, natural stable K isotope ratios-δ41K-of human serum samples were characterized in an AD biomarker pilot study (plus two paired Li-heparin and K-EDTA plasma samples). AD serum was found to have a significantly lower mean δ41K relative to controls. To mechanistically explore this change, novel ab initio calculations (Density Functional Theory, DFT) of relative K isotope compositions between hydrated K+ and organically bound K were performed, identifying hydrated K+ as isotopically light (lower δ41K) compared to organically bound K. Taken together with literature, serum δ41K and DFT results are consistent with efflux of hydrated K+ from the brain to the bloodstream, manifesting a measurable decrease in serum δ41K. These data introduce serum δ41K for further investigation as a minimally invasive AD biomarker, with cost, scalability and stability advantages over current techniques.
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