Melbourne Analytical Geochemistry, School of Geography, Earth and Atmospheric Sciences, University of Melbourne, Melbourne, Australia.
IsoTropics Geochemistry Lab, Earth and Environmental Science, James Cook University, Townsville, Queensland 4814, Australia.
Metallomics. 2024 Sep 5;16(9). doi: 10.1093/mtomcs/mfae038.
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.
阿尔茨海默病（AD）患者大脑中 K 被清除，同时血清 K 增加，表明存在脑-血 K 转移。在此，我们在 AD 生物标志物的初步研究中（另外还有两份配对的锂肝素和钾乙二胺四乙酸 [K-EDTA] 血浆样本），对人血清样本中的天然稳定 K 同位素比值-δ41K 进行了特征描述。与对照组相比，AD 患者血清的平均 δ41K 明显更低。为了从机制上探索这种变化，我们对水合 K+和有机结合 K+之间的相对 K 同位素组成进行了新的从头计算（密度泛函理论），结果表明水合 K+的同位素较轻（δ41K 较低），而有机结合 K+则较重。结合文献，血清 δ41K 和密度泛函理论结果表明，水合 K+从大脑流出到血液中，导致血清 δ41K 可测量下降。这些数据表明，血清 δ41K 可作为一种微创 AD 生物标志物进一步研究，与当前技术相比，具有成本、可扩展性和稳定性优势。
