Mohamed Mohamed A, Zeng Zhou, Gennaro Marta, Lao-Kaim Nicholas P, Myers Jim F M, Calsolaro Valeria, Femminella Grazia Daniela, Tyacke Robin J, Martin-Bastida Antonio, Gunn Roger N, Nutt David J, Edison Paul, Piccini Paola, Roussakis Andreas-Antonios
Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China.
Brain Commun. 2022 Aug 18;4(5):fcac199. doi: 10.1093/braincomms/fcac199. eCollection 2022.
The role of astrogliosis in the pathology of brain aging and neurodegenerative diseases has recently drawn great attention. Imidazoline-2 binding sites represent a possible target to map the distribution of reactive astrocytes. In this study, we use C-BU99008, an imidazoline-2 binding sites-specific PET radioligand, to image reactive astrocytes in healthy controls and patients with established Parkinson's disease dementia. Eighteen healthy controls (age: 45-78 years) and six patients with Parkinson's disease dementia (age: 64-77 years) had one C-BU99008 PET-CT scan with arterial input function. All subjects underwent one 3 T MRI brain scan to facilitate the analysis of the PET data and to capture individual cerebral atrophy. Regional C-BU99008 volumes of distribution were calculated for each subject by the two-tissue compartmental modelling. Positive correlations between C-BU99008 volumes of distribution values and age were found for all tested regions across the brain within healthy controls ( < 0.05); furthermore, multiple regression indicated that aging affects C-BU99008 volumes of distribution values in a region-specific manner. Independent samples -test indicated that there was no significant group difference in C-BU99008 volumes of distribution values between Parkinson's disease dementia ( = 6; mean age = 71.97 ± 4.66 years) and older healthy controls ( = 9; mean age = 71.90 ± 5.51 years). Our data set shows that astrogliosis is common with aging in a region-specific manner. However, in this set-up, C-BU99008 PET cannot differentiate patients with Parkinson's disease dementia from healthy controls of similar age.
星形胶质细胞增生在脑老化和神经退行性疾病病理学中的作用最近备受关注。咪唑啉-2结合位点是描绘反应性星形胶质细胞分布的一个可能靶点。在本研究中，我们使用C-BU99008，一种咪唑啉-2结合位点特异性PET放射性配体，对健康对照者和已确诊帕金森病痴呆患者的反应性星形胶质细胞进行成像。18名健康对照者（年龄：45 - 78岁）和6名帕金森病痴呆患者（年龄：64 - 77岁）接受了一次带有动脉输入函数的C-BU99008 PET-CT扫描。所有受试者均接受一次3T MRI脑部扫描，以促进PET数据的分析并捕捉个体脑萎缩情况。通过双组织房室模型为每个受试者计算C-BU99008的区域分布容积。在健康对照者中，全脑所有测试区域的C-BU99008分布容积值与年龄之间均存在正相关（<0.05）；此外，多元回归表明衰老以区域特异性方式影响C-BU99008分布容积值。独立样本检验表明，帕金森病痴呆患者（n = 6；平均年龄 = 71.97 ± 4.66岁）和老年健康对照者（n = 9；平均年龄 = 71.90 ± 5.51岁）之间的C-BU99008分布容积值无显著组间差异。我们的数据集表明，星形胶质细胞增生在衰老过程中以区域特异性方式常见。然而，在此设置下，C-BU99008 PET无法区分帕金森病痴呆患者和年龄相仿的健康对照者。
