Michele Matarazzo, Alexandra Pérez-Soriano, Nasim Vafai, Elham Shahinfard, Kevin Ju-Chieh Cheng, Jessamyn McKenzie, Nicole Neilson, Qing Miao, Paul Schaffer, Hitoshi Shinotoh, Jeffrey H. Kordower, Vesna Sossi, A. Jon Stoessl
{"title":"Misfolded protein deposits in Parkinson’s disease and Parkinson’s disease-related cognitive impairment, a [11C]PBB3 study","authors":"Michele Matarazzo, Alexandra Pérez-Soriano, Nasim Vafai, Elham Shahinfard, Kevin Ju-Chieh Cheng, Jessamyn McKenzie, Nicole Neilson, Qing Miao, Paul Schaffer, Hitoshi Shinotoh, Jeffrey H. Kordower, Vesna Sossi, A. Jon Stoessl","doi":"10.1038/s41531-024-00708-z","DOIUrl":null,"url":null,"abstract":"<p>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 [<sup>11</sup>C]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 [<sup>11</sup>C]PBB3 PET. A subset of the PD subjects also underwent PET imaging with [<sup>11</sup>C](+)DTBZ to assess dopaminergic denervation and [<sup>11</sup>C]PBR28 to assess neuroinflammation. Compared to HC, PD subjects showed higher [<sup>11</sup>C]PBB3 binding in the posterior putamen but not the substantia nigra. There was no relationship across subjects between [<sup>11</sup>C]PBB3 and [<sup>11</sup>C]PBR28 binding in nigrostriatal regions. [<sup>11</sup>C]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 [<sup>11</sup>C]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.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":6.7000,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NPJ Parkinson's Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41531-024-00708-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
npj Parkinson's Disease is a comprehensive open access journal that covers a wide range of research areas related to Parkinson's disease. It publishes original studies in basic science, translational research, and clinical investigations. The journal is dedicated to advancing our understanding of Parkinson's disease by exploring various aspects such as anatomy, etiology, genetics, cellular and molecular physiology, neurophysiology, epidemiology, and therapeutic development. By providing free and immediate access to the scientific and Parkinson's disease community, npj Parkinson's Disease promotes collaboration and knowledge sharing among researchers and healthcare professionals.