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

Abstract

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 mid-life 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.

Alzheimer’s Disease and Age-Related Changes in the Cu Isotopic Composition of Blood Plasma and Brain Tissues of the APPNL-G-F Murine Model Revealed by Multi-Collector ICP-Mass Spectrometry

“…The most notable effect of AD on Cu concentration was observed in the brain stem, in which both the young and aged mice showed a significant trend towards a higher Cu content. The dysregulated Cu homeostasis in the brain stem of AD transgenic mice could be an indication that the brain stem is affected in an initial stage during the pathogenesis of AD, in contrast to earlier beliefs about the hippocampus that were hypothesized in previous works [54,55]. Although AD does not seem to affect the δ 65 Cu value of the brain stem, age seems to exert a significant effect on the isotopic composition in healthy controls.…”

Analysis of urinary potassium isotopes and association with pancreatic health: healthy, diabetic and cancerous states

“…Mahan et al. ( 8 ) studied the K isotope composition of brains from Göttingen minipigs and its implication by Alzheimer’s disease in humans. K isotope ratios for various minipig brain regions were found to range from −0.80 to −0.34‰, with a variability of ∼0.5‰ between different brain regions.…”

“…It has three naturally occurring isotopes: 39 K (93.258%), 40 K (0.012%) and 41 K (6.730%). To date, although very few studies have done K isotope analysis in biological samples, K isotope ratios have shown much larger variations than geological samples (7)(8)(9). For instance, terrestrial plants show large K isotope differences between C 3 (d 41 K = −1.06 to -0.15‰) and C 4 plants (d 41 K = +0.28 to 1.15‰) (10).…”

“…Moynier et al (7) observed distinct pattern of K isotope ratios in animals with d 41 K varying by ∼1‰ between the bovine blood and organs. Mahan et al (8) studied the K isotope composition of brains from Göttingen minipigs and its implication by Alzheimer's disease in humans. K isotope ratios for various minipig brain regions were found to range from −0.80 to −0.34‰, with a variability of ∼0.5‰ between different brain regions.…”

The Genetic Selection of HSPD1 and HSPE1 Reduce Inflammation of Liver and Spleen While Restraining the Growth and Development of Skeletal Muscle in Wuzhishan Pigs

“…A study comparing splenic artery and neuromodulation between mice, rats, pigs, and humans indicated that the pig was the most suitable model for investigating human splenic innervation [ 5 ]. Göttingen minipigs were implicated in radiation-induced coagulopathy and Alzheimer’s disease recently [ 6 , 7 ]; WZS minipigs were used for an alloxan toxicity test and Islet isolation and purification in a diabetes simulation experiment [ 8 , 9 ]; therefore, minipigs acted as a good model for investigating the human immune system.…”