Stable potassium isotope ratios in human blood serum towards biomarker development in Alzheimer's disease
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.
Authors
- Esther Lahoud (ORCID: https://orcid.org/0009-0007-3009-3235)
- Alex McCoy-West
- Frédéric Moynier (ORCID: https://orcid.org/0000-0003-4321-5581)
- Ashley I. Bush (ORCID: https://orcid.org/0000-0001-8259-9069)
- Yan Hu (ORCID: https://orcid.org/0000-0003-3899-0436)
- Mark Nestmeyer (ORCID: https://orcid.org/0000-0002-6049-444X)
- Brandon Mahan (ORCID: https://orcid.org/0000-0002-5371-0730)
- Christopher Fowler (ORCID: https://orcid.org/0000-0003-1397-0359)
- Grace Manestar
Institutions
- Centre National de la Recherche Scientifique (FR)
- University of Nevada, Las Vegas (US)
- Institut de physique du globe de Paris (FR)
- The University of Melbourne (AU)
- Université Paris Cité (FR)
- Florey Institute of Neuroscience and Mental Health (AU)
- James Cook University (AU)
Publication Details
- Journal
- Metallomics
- Published
- 2024-08-31
- DOI
- https://doi.org/10.1093/mtomcs/mfae038
- Citations
- 3
- Primary Topic
- Amino Acid Enzymes and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.88
Funders
- Alzheimer's Association
- Science and Industry Endowment Fund
- Strong
- Commonwealth Scientific and Industrial Research Organisation
- Agence Nationale de la Recherche
- Edith Cowan University
- Dementia Collaborative Research Centres, Australia
- State Government of Victoria
- Institut de Physique du Globe de Paris
- Université de Paris
- Medical Research Council
- National Health and Medical Research Council