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.
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。