Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
Mov Disord. 2024 Jul;39(7):1166-1178. doi: 10.1002/mds.29814. Epub 2024 Apr 26.
BACKGROUND/OBJECTIVE: The corticobasal syndrome (CBS) is a complex asymmetric movement disorder, with cognitive impairment. Although commonly associated with the primary 4-repeat-tauopathy of corticobasal degeneration, clinicopathological correlation is poor, and a significant proportion is due to Alzheimer's disease (AD). Synaptic loss is a pathological feature of many clinical and preclinical tauopathies. We therefore measured the degree of synaptic loss in patients with CBS and tested whether synaptic loss differed according to β-amyloid status.
Twenty-five people with CBS, and 32 age-/sex-/education-matched healthy controls participated. Regional synaptic density was estimated by [C]UCB-J non-displaceable binding potential (BP), AD-tau pathology by [F]AV-1451 BP, and gray matter volume by T1-weighted magnetic resonance imaging. Participants with CBS had β-amyloid imaging with C-labeled Pittsburgh Compound-B ([C]PiB) positron emission tomography. Symptom severity was assessed with the progressive supranuclear palsy-rating-scale, the cortical basal ganglia functional scale, and the revised Addenbrooke's Cognitive Examination. Regional differences in BP and gray matter volume between groups were assessed by ANOVA.
Compared to controls, patients with CBS had higher [F]AV-1451 uptake, gray matter volume loss, and reduced synaptic density. Synaptic loss was more severe and widespread in the β-amyloid negative group. Asymmetry of synaptic loss was in line with the clinically most affected side.
Distinct patterns of [C]UCB-J and [F]AV-1451 binding and gray matter volume loss, indicate differences in the pathogenic mechanisms of CBS according to whether it is associated with the presence of Alzheimer's disease or not. This highlights the potential for different therapeutic strategies in CBSs. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
背景/目的：皮质基底节综合征（CBS）是一种复杂的不对称运动障碍，伴有认知障碍。尽管通常与皮质基底节变性的原发性 4 重复tau 病有关，但临床病理相关性较差，且很大一部分是由于阿尔茨海默病（AD）。突触丢失是许多临床和临床前tau 病的病理特征。因此，我们测量了 CBS 患者的突触丢失程度，并测试了突触丢失是否因β-淀粉样蛋白状态而异。
25 名 CBS 患者和 32 名年龄/性别/教育匹配的健康对照者参与了研究。通过 [C]UCB-J 不可置换结合潜能（BP）估计区域突触密度，通过 [F]AV-1451 BP 估计 AD-tau 病理学，通过 T1 加权磁共振成像估计灰质体积。使用 C 标记的匹兹堡化合物-B（[C]PiB）正电子发射断层扫描对 CBS 患者进行β-淀粉样蛋白成像。使用进行性核上性麻痹评分量表、皮质基底节功能量表和修订后的 Addenbrooke 认知测验评估症状严重程度。通过方差分析评估组间 BP 和灰质体积的区域差异。
与对照组相比，CBS 患者的 [F]AV-1451 摄取量、灰质体积损失和突触密度降低更高。在β-淀粉样蛋白阴性组中，突触丢失更为严重且广泛。突触丢失的不对称性与临床上最受影响的一侧一致。
[C]UCB-J 和 [F]AV-1451 结合以及灰质体积损失的不同模式表明，根据 CBS 是否与阿尔茨海默病的存在有关，其发病机制存在差异。这突出了在 CBS 中采用不同治疗策略的潜力。© 2024 作者。运动障碍由 Wiley 期刊公司代表国际帕金森病和运动障碍协会出版。
