Exploring the K isotope composition of Gottingen minipig brain regions, and implications for Alzheimer's disease

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 Gottingen minipig brain regions for two AD models at midlife are reported. Results indicate heavy K isotope enrichment where amyloid beta (A beta) 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 A beta (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.

Automated summary

Natural stable metal isotopes have shown potential in differentiating healthy and diseased brain states. Alzheimer's disease brains expel potassium, which is accompanied by increased serum potassium levels. Heavy potassium isotope enrichment is observed in the regions of amyloid beta accumulation, which correlates with potassium depletion. The composition of potassium isotopes in the brain differs from that in serum, suggesting the generation of an early Alzheimer's disease biomarker.