Introduction

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder with diverse clinical presentations that are linked to tau pathology. Recently, Subtype and Stage Inference (SuStaIn) algorithm, an innovative data-driven method, has been developed to model both the spatial-temporal progression and subtypes of disease. This study explores PSP progression using ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging and the SuStaIn algorithm to identify PSP metabolic progression subtypes and understand disease mechanisms.

Methods

The study included 72 PSP patients and 70 controls, with an additional 24 PSP patients enrolled as a test set, undergoing FDG-PET, dopamine transporter (DAT) PET, and neuropsychological assessments. The SuStaIn algorithm was employed to analyze the FDG-PET data, identifying progression subtypes and sequences.

Results

Two PSP subtypes were identified: the cortical subtype with early prefrontal hypometabolism and the brainstem subtype with initial midbrain alterations. The cortical subtype displayed greater cognitive impairment and DAT reduction than the brainstem subtype. The test set demonstrates the robustness and reproducibility of the findings. Pathway analysis indicated that disruptions in dopaminergic cortico-basal ganglia pathways are crucial for elucidating the mechanisms of cognitive and behavioral impairment in PSP, leading to the two metabolic progression subtypes.

Conclusion

This study identified two spatiotemporal progression subtypes of PSP based on FDG-PET imaging, revealing significant differences in metabolic patterns, striatal dopaminergic uptake, and clinical profiles, particularly cognitive impairments. The findings highlight the crucial role of dopaminergic cortico-basal ganglia pathways in PSP pathophysiology, especially in the cortical subtype, providing insights into PSP heterogeneity and potential avenues for personalized treatments.

中文翻译：

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通过 PET 分子成像识别进行性核上性麻痹的代谢进展和亚型

 介绍

进行性核上性麻痹 （PSP） 是一种神经退行性疾病，具有与 tau 病理相关的多种临床表现。最近，亚型和阶段推理 （SuStaIn） 算法是一种创新的数据驱动方法，已被开发用于对疾病的时空进展和亚型进行建模。本研究使用 ¹⁸F 氟脱氧葡萄糖 （FDG） 正电子发射断层扫描 （PET） 成像和 SuStaIn 算法探索 PSP 进展，以识别 PSP 代谢进展亚型并了解疾病机制。

 方法

该研究包括 72 名 PSP 患者和 70 名对照患者，另有 24 名 PSP 患者作为测试集入组，接受 FDG-PET、多巴胺转运蛋白 （DAT） PET 和神经心理学评估。采用 SuStaIn 算法分析 FDG-PET 数据，识别进展亚型和序列。

 结果

确定了两种 PSP 亚型：具有早期前额叶代谢减退的皮质亚型和具有初始中脑改变的脑干亚型。皮质亚型比脑干亚型表现出更大的认知障碍和 DAT 降低。该测试集证明了结果的稳健性和可重复性。通路分析表明，多巴胺能皮质-基底神经节通路的破坏对于阐明 PSP 认知和行为障碍的机制至关重要，从而导致两种代谢进展亚型。

 结论

本研究基于 FDG-PET 成像确定了 PSP 的两种时空进展亚型，揭示了代谢模式、纹状体多巴胺能摄取和临床特征（尤其是认知障碍）的显着差异。这些发现强调了多巴胺能皮质基底神经节通路在 PSP 病理生理学中的关键作用，尤其是在皮质亚型中，为 PSP 异质性和个性化治疗的潜在途径提供了见解。