Objective: In addition to tau pathology and neuronal loss, neuroinflammation occurs in progressive supranuclear palsy (PSP). We test the hypotheses that baseline in vivo assessments of regional neuroinflammation ([¹¹C]PK11195 PET), tau pathology ([¹⁸F]AV-1451 PET), and atrophy (structural MRI) predict disease progression. Methods: Seventeen patients with PSP-Richardson′s syndrome underwent a baseline multi-modal imaging assessment. Disease severity was measured at baseline and serially up to 4 years with the PSP-rating-scale (average interval 5 months). Regional grey-matter volumes and PET ligand binding potentials were summarised by three Principal Component Analyses (PCAs). A linear mixed effects model was applied to the longitudinal PSP-rating-scale scores. Single-modality imaging predictors were regressed against the individuals′ estimated rate of progression to identify the prognostic value of baseline imaging markers. Results: The PCA factors reflecting neuroinflammation and tau burden in the brainstem and cerebellum correlated with the subsequent annual rate of change in the PSP-rating-scale. PCA-derived PET markers of neuroinflammation and tau pathology correlated with brain atrophy in the same regions. However, MRI markers of brain atrophy alone did not predict clinical progression. Conclusions: Molecular imaging with PET can predict clinical progression in PSP. These data encourage the evaluation of immunomodulatory approaches to disease-modifying therapies in PSP, and the potential for PET to stratify patients for early phase clinical trials.

中文翻译：

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神经炎症可预测进行性核上性麻痹的疾病进展

目的：除了tau病理和神经元丢失外，进行性核上性麻痹（PSP）还会发生神经炎症。我们测试了以下假设：基线体内评估局部神经炎症（[ ¹¹ C] PK11195 PET），tau病理（[ ¹⁸F] AV-1451 PET）和萎缩（结构MRI）可预测疾病进展。方法：对17例PSP-Richardson综合征患者进行了基线多模式影像学评估。疾病严重程度在基线时进行测量，并连续4年使用PSP评分量表（平均间隔5个月）进行测量。通过三个主成分分析（PCA）总结了区域灰物质的体积和PET配体的结合潜力。将线性混合效应模型应用于纵向PSP评分量表分数。将单模态成像预测因子与个体的估计进展率进行回归，以识别基线成像标志物的预后价值。结果：反映脑干和小脑中神经炎症和tau负担的PCA因子与随后的PSP评分量表的年变化率相关。PCA衍生的神经炎症和tau病理的PET标志物与相同区域的脑萎缩相关。但是，仅脑萎缩的MRI标记不能预测临床进展。结论：PET分子成像可以预测PSP的临床进展。这些数据鼓励对免疫调节方法进行PSP疾病改变疗法的评估，以及PET在早期临床试验中对患者进行分层的潜力。PET分子成像可以预测PSP的临床进展。这些数据鼓励对免疫调节方法进行PSP疾病改变疗法的评估，以及PET在早期临床试验中对患者进行分层的潜力。PET分子成像可以预测PSP的临床进展。这些数据鼓励对免疫调节方法进行PSP疾病改变疗法的评估，以及PET在早期临床试验中对患者进行分层的潜力。