Understanding the cellular underpinnings of neurodegeneration remains a challenge; loss of synapses and dendritic arborisation are characteristic and can be quantified in vivo, with [¹¹C]UCB-J PET and MRI-based Orientation Dispersion Imaging (ODI), respectively. We aimed to assess how both measures are correlated, in 4R-tauopathies of Progressive Supranuclear Palsy (PSP-RS; n = 22) and amyloid-negative (determined by [11C]PiB PET) Corticobasal Degeneration (CBD; n =14), as neurodegenerative disease models, in this proof-of-concept study. Compared to controls (n = 27), PSP-RS and CBD patients had widespread reductions in cortical ODI, and [¹¹C]UCB-J non-displaceable binding potential (BP _ND) in excess of atrophy. In PSP-RS and CBD separately, regional cortical ODI was significantly associated with [¹¹C]UCB-J BP_ND in disease-associated regions (p < 0.05, FDR corrected). Our findings indicate that reductions in synaptic density and dendritic complexity in PSP-RS and CBD are more severe and extensive than atrophy. Furthermore, both measures are tightly coupled in vivo, furthering our understanding of the pathophysiology of neurodegeneration, and applicable to studies of early neurodegeneration with a safe and widely available MRI platform.

中文翻译：

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树突状复杂性与原发性颅骨病变中突触前密度的体内偶联

了解神经变性的细胞基础仍然是一个挑战。突触的丢失和树突状乔木化是特征性的，可以分别在体内进行定量[ ¹¹ C] UCB-J PET和基于MRI的定向分散成像（ODI）。我们旨在评估渐进性核上性麻痹（PSP-RS； n = 22）和淀粉样蛋白阴性（由[11C] PiB PET确定）皮质基底变性（CBD; n = 14）的4R病态，两种措施之间的相关性，在概念验证研究中，作为神经退行性疾病模型。与对照组相比（n = 27），PSP-RS和CBD患者的皮质ODI广泛降低，[ ¹¹ C] UCB-J不可取代的结合潜力（BP _ND）超过萎缩。在疾病相关地区，分别在PSP-RS和CBD中，区域皮质ODI与[ ¹¹ C] UCB-J BP _ND显着相关（p <0.05，经FDR校正）。我们的研究结果表明，PSP-RS和CBD中突触密度和树突复杂性的降低比萎缩更为严重和广泛。此外，这两种措施在体内紧密耦合，进一步加深了我们对神经变性的病理生理学的了解，并适用于使用安全且广泛可用的MRI平台进行早期神经变性的研究。