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

Journal Publication ResearchOnline@JCU
Mahan, Brandon;Hu, Yan;Lahoud, Esther;Nestmeyer, Mark;McCoy-West, Alex;Manestar, Grace;Fowler, Christopher;Bush, Ashley I.;Moynier, Frédéric
Abstract

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 potassium ethylenediaminetetraacetic acid [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) 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 density functional theory 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.

Journal

Metallomics

Publication Name

Metallomics

Volume

16

ISBN/ISSN

1756-591X

Edition

N/A

Issue

9

Pages Count

10

Location

N/A

Publisher

Oxford University Press

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Publisher Location

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Publish Date

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Url

N/A

Date

N/A

EISSN

N/A

DOI

10.1093/mtomcs/mfae038