Natural stable metal isotopes have shown utility in differentiation between healthy and diseased brain states (e.g. Alzheimer's disease, AD). While the AD brain accumulates some metals, it purges others, namely K (accompanied by increased serum K, suggesting brain-blood transferal). Here, K isotope compositions of Göttingen minipig brain regions for two AD models at midlife are reported. Results indicate heavy K isotope enrichment where amyloid beta (Aβ) accumulation is observed, and this enrichment correlates with relative K depletion. These results suggest preferential efflux of isotopically light K+ from the brain, a linkage between brain K concentrations and isotope compositions, and linkage to Aβ (previously shown to purge cellular brain K+). Brain K isotope compositions differ from that for serum and brain K is much more abundant than in serum, suggesting that changes in brain K may transfer a measurable K isotope excursion to serum, thereby generating an early AD biomarker.
Keywords: Alzheimer's disease, brain potassium; isotope geochemistry; isotope metallomics; neurodegeneration, porcine model.
© The Author(s) 2022.Published by Oxford University Press.