β-Amyloid plaques and tau-containing neurofibrillary tangles are the two neuropathological hallmarks of Alzheimer's disease (AD) and are thought to play crucial roles in a neurodegenerative cascade leading to dementia. Both lesions can now be visualized in vivo using positron emission tomography (PET) radiotracers, opening new opportunities to study disease mechanisms and improve patients' diagnostic and prognostic evaluation. In a group of 32 patients at early symptomatic AD stages, we tested whether β-amyloid and tau-PET could predict subsequent brain atrophy measured using longitudinal magnetic resonance imaging acquired at the time of PET and 15 months later. Quantitative analyses showed that the global intensity of tau-PET, but not β-amyloid-PET, signal predicted the rate of subsequent atrophy, independent of baseline cortical thickness. Additional investigations demonstrated that the specific distribution of tau-PET signal was a strong indicator of the topography of future atrophy at the single patient level and that the relationship between baseline tau-PET and subsequent atrophy was particularly strong in younger patients. These data support disease models in which tau pathology is a major driver of local neurodegeneration and highlight the relevance of tau-PET as a precision medicine tool to help predict individual patient's progression and design future clinical trials.

中文翻译：

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阿尔茨海默病的预期纵向萎缩与基线 tau-PET 的强度和形态相关。


β-淀粉样斑块和含有 tau 蛋白的神经原纤维缠结是阿尔茨海默病 (AD) 的两个神经病理学标志，被认为在导致痴呆的神经退行性级联反应中发挥着至关重要的作用。现在可以使用正电子发射断层扫描 (PET) 放射性示踪剂在体内对这两种病变进行可视化，从而为研究疾病机制和改善患者的诊断和预后评估提供了新的机会。在一组 32 名处于早期症状 AD 阶段的患者中，我们测试了 β-淀粉样蛋白和 tau-PET 是否可以预测随后的脑萎缩，使用 PET 时和 15 个月后获得的纵向磁共振成像进行测量。定量分析表明，tau-PET（而非 β-淀粉样蛋白-PET）信号的整体强度可以预测随后的萎缩率，与基线皮质厚度无关。其他研究表明，tau-PET 信号的特定分布是单个患者水平未来萎缩形态的有力指标，并且基线 tau-PET 与随后的萎缩之间的关系在年轻患者中尤其强烈。这些数据支持疾病模型，其中 tau 病理学是局部神经变性的主要驱动因素，并强调 tau-PET 作为精准医学工具的相关性，有助于预测个体患者的进展和设计未来的临床试验。