In Alzheimer's disease, brain amyloid deposition has a distinct topography that correlates with aerobic glycolysis (AG), that is, the use of glucose beyond that predicted by oxygen consumption. The causes for this relationship remain unclear but might provide crucialinsight into how amyloid deposition begins. Here we develop methods to study the earliest topography of amyloid deposition based on amyloid imaging and investigate its spatiotemporal evolution with respect to the topography of AG in adults. We find that the spatiotemporal dynamics of amyloid deposition are largely explained by 1 factor, defined here as the amyloid topography dissimilarity index (ATDI). ATDI is bimodal, more highly dynamic during early amyloid accumulation, and predicts which individuals will cross a conservative quantitative threshold at least 3-5 years in advance. Using ATDI, we demonstrate that subthreshold amyloid accumulates primarily in regions that have high AG during early adulthood. Our findings suggest that early on-target subthreshold amyloid deposition mirrors its later regional pattern, which best corresponds to the topography of young adult brain AG.

中文翻译：

---

人脑亚阈下淀粉样蛋白积累与有氧糖酵解的时空关系

在阿尔茨海默病中，大脑淀粉样蛋白沉积具有与有氧糖酵解 (AG) 相关的独特形态，也就是说，葡萄糖的使用超出了耗氧量的预测。这种关系的原因尚不清楚，但可能会提供有关淀粉样蛋白沉积如何开始的重要见解。在这里，我们开发了基于淀粉样蛋白成像研究最早的淀粉样蛋白沉积地形的方法，并研究其相对于成人 AG 地形的时空演变。我们发现淀粉样蛋白沉积的时空动态主要由 1 个因素解释，这里定义为淀粉样蛋白地形差异指数 (ATDI)。ATDI 是双峰的，在早期淀粉样蛋白积累期间更具动态性，并预测哪些个体将至少提前 3-5 年跨越保守的定量阈值。使用 ATDI，我们证明阈下淀粉样蛋白主要在成年早期具有高 AG 的区域积累。我们的研究结果表明，早期的目标亚阈值淀粉样蛋白沉积反映了其后期的区域模式，这最符合年轻成人大脑 AG 的地形。