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神经炎症与 Tau 蛋白在进行性核上性麻痹的体内共定位。

Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy.

机构信息

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Institute of Molecular Bioimaging and Physiology, National Research Council, Milan, Italy.

出版信息

Ann Neurol. 2020 Dec;88(6):1194-1204. doi: 10.1002/ana.25911. Epub 2020 Oct 10.

DOI:10.1002/ana.25911
PMID:32951237
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7116392/
Abstract

OBJECTIVE

We examined the relationship between tau pathology and neuroinflammation using [ C]PK11195 and [ F]AV-1451 PET in 17 patients with progressive supranuclear palsy (PSP) Richardson's syndrome. We tested the hypothesis that neuroinflammation and tau protein aggregation colocalize macroscopically, and correlate with clinical severity.

METHODS

Nondisplaceable binding potential (BP ) for each ligand was quantified in 83 regions of interest (ROIs). The [ C]PK11195 and [ F]AV-1451 BP values were correlated across all regions. The spatial distributions of [ C]PK11195 and [ F]AV-1451 binding were determined by principal component analyses (PCAs), and the loading of each spatial component compared against the patients' clinical severity (using the PSP rating scale).

RESULTS

Regional [ C]PK11195 and [ F]AV-1451 binding were positively correlated (R = 0.577, p < 0.0001). The PCA identified 4 components for each ligand, reflecting the relative expression of tau pathology or neuroinflammation in distinct groups of brain regions. Positive associations between [ C]PK11195 and [ F]AV-1451 components' loadings were found in both subcortical (R = 0.769, p < 0.0001) and cortical regions (R = 0.836, p < 0.0001). There were positive correlations between clinical severity and both subcortical tau pathology (R = 0.667, p = 0.003) and neuroinflammation (R = 0.788, p < 0.001).

INTERPRETATION

We show that tau pathology and neuroinflammation colocalize in PSP, and that individual differences in subcortical tau pathology and neuroinflammation are linked to clinical severity. Although longitudinal studies are needed to determine causal associations between these molecular pathologies, we suggest that the combination of tau- and immune-oriented strategies may be useful for effective disease-modifying treatments in PSP. ANN NEUROL 2020;88:1194-1204.

摘要

目的

我们使用 [C]PK11195 和 [F]AV-1451 PET 对 17 例进行性核上性麻痹(PSP)Richardson 综合征患者的 tau 病理学和神经炎症之间的关系进行了研究。我们检验了以下假说:神经炎症和 tau 蛋白聚集在宏观上是共定位的,并且与临床严重程度相关。

方法

在 83 个感兴趣区域(ROI)中定量测定了每种配体的不可置换结合潜能(BP)。所有区域均对 [C]PK11195 和 [F]AV-1451 BP 值进行了相关性分析。通过主成分分析(PCA)确定了 [C]PK11195 和 [F]AV-1451 结合的空间分布,并用患者的临床严重程度(使用 PSP 评定量表)对每个空间分量的负荷进行了比较。

结果

区域性 [C]PK11195 和 [F]AV-1451 结合呈正相关(R = 0.577,p < 0.0001)。PCA 为每种配体确定了 4 个分量,反映了 tau 病理学或神经炎症在不同脑区的相对表达。在皮质下(R = 0.769,p < 0.0001)和皮质区域(R = 0.836,p < 0.0001)中均发现 [C]PK11195 和 [F]AV-1451 分量的负荷之间存在正相关。临床严重程度与皮质下 tau 病理学(R = 0.667,p = 0.003)和神经炎症(R = 0.788,p < 0.001)均呈正相关。

结论

我们表明 tau 病理学和神经炎症在 PSP 中是共定位的,皮质下 tau 病理学和神经炎症的个体差异与临床严重程度相关。尽管需要进行纵向研究以确定这些分子病理学之间的因果关系,但我们认为 tau 定向和免疫定向策略的联合可能对 PSP 的有效疾病修饰治疗有用。

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