Parkinson’s disease (PD) is associated with aggregation of misfolded α-synuclein and other proteins, including tau. We designed a cross-sectional study to quantify the brain binding of [¹¹C]PBB3 (a ligand known to bind to misfolded tau and possibly α-synuclein) as a proxy of misfolded protein aggregation in Parkinson’s disease (PD) subjects with and without cognitive impairment and healthy controls (HC). In this cross-sectional study, nineteen cognitively normal PD subjects (CN-PD), thirteen cognitively impaired PD subjects (CI-PD) and ten HC underwent [¹¹C]PBB3 PET. A subset of the PD subjects also underwent PET imaging with [¹¹C](+)DTBZ to assess dopaminergic denervation and [¹¹C]PBR28 to assess neuroinflammation. Compared to HC, PD subjects showed higher [¹¹C]PBB3 binding in the posterior putamen but not the substantia nigra. There was no relationship across subjects between [¹¹C]PBB3 and [¹¹C]PBR28 binding in nigrostriatal regions. [¹¹C]PBB3 binding was increased in the anterior cingulate in CI-PD compared to CN-PD and HC, and there was an inverse correlation between cognitive scores and [¹¹C]PBB3 binding in this region across all PD subjects. Our results support a primary role of abnormal protein deposition localized to the posterior putamen in PD. This suggests that striatal axonal terminals are preferentially involved in the pathophysiology of PD. Furthermore, our findings suggest that anterior cingulate pathology might represent a significant in vivo marker of cognitive impairment in PD, in agreement with previous neuropathological studies.

帕金森病 (PD) 与错误折叠的 α-突触核蛋白和其他蛋白质（包括 tau）的聚集有关。我们设计了一项横断面研究来量化[ ^11C ]PBB3（一种已知与错误折叠的 tau 蛋白和可能的 α-突触核蛋白结合的配体）的大脑结合，作为帕金森病 (PD) 受试者中错误折叠蛋白聚集的代表。认知障碍和健康对照（HC）。在这项横断面研究中，19 名认知正常的 PD 受试者 (CN-PD)、13 名认知受损的 PD 受试者 (CI-PD) 和 10 名 HC 接受了 [ ¹¹ C]PBB3 PET。一部分 PD 受试者还接受了 PET 成像，使用 [ ¹¹ C](+)DTBZ 评估多巴胺能去神经，并使用 [ ¹¹ C]PBR28 评估神经炎症。与 HC 相比，PD 受试者在后壳核中显示出更高的 [ ^{11 C]PBB3 结合，但在黑质中却没有。黑质纹状体区域的[ 11} C]PBB3 和[ ¹¹ C]PBR28结合在受试者之间没有关系。与 CN-PD 和 HC 相比，CI-PD 中前扣带回的[ ^{11 C]PBB3 结合增加，并且所有 PD 受试者的认知评分与该区域的 [ 11} C]PBB3 结合之间存在负相关。我们的结果支持位于后壳核的异常蛋白质沉积在帕金森病中的主要作用。这表明纹状体轴突末梢优先参与 PD 的病理生理学。此外，我们的研究结果表明，前扣带回病理学可能代表 PD 认知障碍的重要体内标志物，与之前的神经病理学研究一致。