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Abstract：
Synaptic loss is a prominent and early feature of many neurodegenerative diseases.
We tested the hypothesis that synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) (Richardson\'s syndrome) and amyloid-negative corticobasal syndrome (CBS).
Forty-four participants (15 CBS, 14 PSP, and 15 age-/sex-/education-matched controls) underwent PET with the radioligand [11 C]UCB-J, which binds to synaptic vesicle glycoprotein 2A, a marker of synaptic density; participants also had 3 Tesla MRI and clinical and neuropsychological assessment.
Nine CBS patients had negative amyloid biomarkers determined by [11 C]PiB PET and hence were deemed likely to have corticobasal degeneration (CBD). Patients with PSP-Richardson\'s syndrome and amyloid-negative CBS were impaired in executive, memory, and visuospatial tasks. [11 C]UCB-J binding was reduced across frontal, temporal, parietal, and occipital lobes, cingulate, hippocampus, insula, amygdala, and subcortical structures in both PSP and CBD patients compared to controls (P < 0.01), with median reductions up to 50%, consistent with postmortem data. Reductions of 20% to 30% were widespread even in areas of the brain with minimal atrophy. There was a negative correlation between global [11 C]UCB-J binding and the PSP and CBD rating scales (R = -0.61, P < 0.002; R = -0.72, P < 0.001, respectively) and a positive correlation with the revised Addenbrooke\'s Cognitive Examination (R = 0.52; P = 0.01).
We confirm severe synaptic loss in PSP and CBD in proportion to disease severity, providing critical insight into the pathophysiology of primary degenerative tauopathies. [11 C]UCB-J may facilitate treatment strategies for disease-modification, synaptic maintenance, or restoration. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
We tested the hypothesis that synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) (Richardson\'s syndrome) and amyloid-negative corticobasal syndrome (CBS).
Forty-four participants (15 CBS, 14 PSP, and 15 age-/sex-/education-matched controls) underwent PET with the radioligand [11 C]UCB-J, which binds to synaptic vesicle glycoprotein 2A, a marker of synaptic density; participants also had 3 Tesla MRI and clinical and neuropsychological assessment.
Nine CBS patients had negative amyloid biomarkers determined by [11 C]PiB PET and hence were deemed likely to have corticobasal degeneration (CBD). Patients with PSP-Richardson\'s syndrome and amyloid-negative CBS were impaired in executive, memory, and visuospatial tasks. [11 C]UCB-J binding was reduced across frontal, temporal, parietal, and occipital lobes, cingulate, hippocampus, insula, amygdala, and subcortical structures in both PSP and CBD patients compared to controls (P < 0.01), with median reductions up to 50%, consistent with postmortem data. Reductions of 20% to 30% were widespread even in areas of the brain with minimal atrophy. There was a negative correlation between global [11 C]UCB-J binding and the PSP and CBD rating scales (R = -0.61, P < 0.002; R = -0.72, P < 0.001, respectively) and a positive correlation with the revised Addenbrooke\'s Cognitive Examination (R = 0.52; P = 0.01).
We confirm severe synaptic loss in PSP and CBD in proportion to disease severity, providing critical insight into the pathophysiology of primary degenerative tauopathies. [11 C]UCB-J may facilitate treatment strategies for disease-modification, synaptic maintenance, or restoration. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
摘要：
突触丢失是许多神经退行性疾病的突出和早期特征。
我们测试了以下假设：进行性核上性麻痹（PSP）（Richardson综合征）和淀粉样蛋白阴性皮质基底综合征（CBS）的原发性tau蛋白病变中突触密度降低。
44名参与者(15名CBS，14PSP,和15个年龄/性别/教育匹配的对照）用放射性配体[11C]UCB-J进行PET，与突触囊泡糖蛋白2A结合，突触密度的标志物;参与者还进行了3TeslaMRI以及临床和神经心理学评估。
九名CBS患者具有通过[11C]PiBPET测定的阴性淀粉样蛋白生物标志物,因此被认为可能具有皮质基底变性(CBD)。PSP-Richardson综合征和淀粉样蛋白阴性CBS的患者在执行方面受损，记忆,和视觉空间任务。[11C]UCB-J结合在额叶上减少，temporal,顶叶,和枕叶，扣带回,海马体,脑岛,杏仁核,与对照组相比，PSP和CBD患者的皮质下结构（P<0.01），中位数下降高达50%，与验尸数据一致。即使在萎缩程度最小的大脑区域，也普遍减少20％至30％。总体[11C]UCB-J结合与PSP和CBD评分量表之间呈负相关（R=-0.61，P<0.002；R=-0.72，P<0.001），与修订后的Addenbrooke认知检查呈正相关（R=0.52；P=0.01）。
我们确认PSP和CBD的严重突触丢失与疾病严重程度成正比，提供对原发性退行性tau蛋白病的病理生理学的关键见解。[11C]UCB-J可以促进疾病修饰的治疗策略，突触维持,或恢复。©2020作者由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
我们测试了以下假设：进行性核上性麻痹（PSP）（Richardson综合征）和淀粉样蛋白阴性皮质基底综合征（CBS）的原发性tau蛋白病变中突触密度降低。
44名参与者(15名CBS，14PSP,和15个年龄/性别/教育匹配的对照）用放射性配体[11C]UCB-J进行PET，与突触囊泡糖蛋白2A结合，突触密度的标志物;参与者还进行了3TeslaMRI以及临床和神经心理学评估。
九名CBS患者具有通过[11C]PiBPET测定的阴性淀粉样蛋白生物标志物,因此被认为可能具有皮质基底变性(CBD)。PSP-Richardson综合征和淀粉样蛋白阴性CBS的患者在执行方面受损，记忆,和视觉空间任务。[11C]UCB-J结合在额叶上减少，temporal,顶叶,和枕叶，扣带回,海马体,脑岛,杏仁核,与对照组相比，PSP和CBD患者的皮质下结构（P<0.01），中位数下降高达50%，与验尸数据一致。即使在萎缩程度最小的大脑区域，也普遍减少20％至30％。总体[11C]UCB-J结合与PSP和CBD评分量表之间呈负相关（R=-0.61，P<0.002；R=-0.72，P<0.001），与修订后的Addenbrooke认知检查呈正相关（R=0.52；P=0.01）。
我们确认PSP和CBD的严重突触丢失与疾病严重程度成正比，提供对原发性退行性tau蛋白病的病理生理学的关键见解。[11C]UCB-J可以促进疾病修饰的治疗策略，突触维持,或恢复。©2020作者由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
