Biometals play a critical role in both the healthy and diseased brain's functioning. They accumulate in the normal aging brain, and are inherent to neurodegenerative disorders and their associated pathologies. A prominent example of this is the brain accumulation of metals such as Ca, Fe and Cu (and more ambiguously, Zn) associated with Alzheimer's disease (AD). The natural stable isotope compositions of such metals have also shown utility in constraining biological mechanisms, and in differentiating between healthy and diseased states, sometimes prior to conventional methods. Here we have detailed the distribution of the biologically relevant elements Mg, P, K, Ca, Fe, Cu and Zn in brain regions of Göttingen minipigs ranging in age from three months to nearly six years, including control animals and both a single- and double-transgenic model of AD (PS1, APP/PS1). Moreover, we have characterized the Ca isotope composition of the brain for the first time. Concentration data track rises in brain biometals with age, namely for Fe and Cu, as observed in the normal ageing brain and in AD, and biometal data point to increased soluble amyloid beta (Aβ) load prior to AD plaque identification via brain imaging. Calcium isotope results define the brain as the isotopically lightest permanent reservoir in the body, indicating that brain Ca dyshomeostasis may induce measurable isotopic disturbances in accessible downstream reservoirs such as biofluids.

中文翻译：

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哥廷根小型猪脑的纵向生物金属积累和钙同位素组成

生物金属在健康和患病大脑的功能中都发挥着关键作用。它们在正常老化的大脑中积累，并且是神经退行性疾病及其相关病理所固有的。一个突出的例子是大脑中与阿尔茨海默病 (AD) 相关的 Ca、Fe 和 Cu（更确切地说是 Zn）等金属的积累。这些金属的天然稳定同位素组成也显示出在限制生物机制和区分健康和疾病状态方面的效用，有时在常规方法之前。在这里，我们详细介绍了年龄从 3 个月到近 6 岁不等的哥廷根小型猪大脑区域中生物相关元素 Mg、P、K、Ca、Fe、Cu 和 Zn 的分布，包括对照动物和 AD 的单转基因和双转基因模型（PS1、APP/PS1）。此外，我们首次表征了大脑的 Ca 同位素组成。大脑生物金属的浓度数据跟踪随年龄增加，即 Fe 和 Cu，如在正常老化大脑和 AD 中观察到的，生物金属数据表明在 AD 斑块识别之前增加了可溶性淀粉样蛋白 (Aβ) 负荷通过脑成像。钙同位素结果将大脑定义为体内同位素最轻的永久性储库，这表明大脑钙稳态失调可能会在可接近的下游储库（如生物流体）中引起可测量的同位素干扰。