Ghadery Christine, Koshimori Yuko, Coakeley Sarah, Harris Madeleine, Rusjan Pablo, Kim Jinhee, Houle Sylvain, Strafella Antonio P
Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Ontario, Canada.
J Neuroinflammation. 2017 Jan 11;14(1):8. doi: 10.1186/s12974-016-0778-1.
Neuroinflammatory processes including activated microglia have been reported to play an important role in Parkinson's disease (PD). Increased expression of translocator protein (TSPO) has been observed after brain injury and inflammation in neurodegenerative diseases. Positron emission tomography (PET) radioligand targeting TSPO allows for the quantification of neuroinflammation in vivo.
Based on the genotype of the rs6791 polymorphism in the TSPO gene, we included 25 mixed-affinity binders (MABs) (14 PD patients and 11 age-matched healthy controls (HC)) and 27 high-affinity binders (HABs) (16 PD patients and 11 age-matched HC) to assess regional differences in the second-generation radioligand [F]-FEPPA between PD patients and HC. FEPPA total distribution volume (V ) values in cortical as well as subcortical brain regions were derived from a two-tissue compartment model with arterial plasma as an input function.
Our results revealed a significant main effect of genotype on [F]-FEPPA V in every brain region, but no main effect of disease or disease × genotype interaction in any brain region. The overall percentage difference of the mean FEPPA V between HC-MABs and HC-HABs was 32.6% (SD = 2.09) and for PD-MABs and PD-HABs was 43.1% (SD = 1.21).
Future investigations are needed to determine the significance of [F]-FEPPA as a biomarker of neuroinflammation as well as the importance of the rs6971 polymorphism and its clinical consequence in PD.
据报道，包括活化小胶质细胞在内的神经炎症过程在帕金森病（PD）中起重要作用。在神经退行性疾病的脑损伤和炎症后，已观察到转位蛋白（TSPO）表达增加。靶向TSPO的正电子发射断层扫描（PET）放射性配体可在体内定量神经炎症。
基于TSPO基因rs6791多态性的基因型，我们纳入了25名混合亲和力结合剂（MABs）（14名PD患者和11名年龄匹配的健康对照（HC））和27名高亲和力结合剂（HABs）（16名PD患者和11名年龄匹配的HC），以评估第二代放射性配体[F]-FEPPA在PD患者和HC之间的区域差异。皮质以及皮质下脑区的FEPPA总分布容积（V）值来自以动脉血浆为输入函数的双组织室模型。
我们的结果显示，基因型对每个脑区的[F]-FEPPA V有显著的主效应，但在任何脑区疾病或疾病×基因型交互作用均无主效应。HC-MABs与HC-HABs之间平均FEPPA V的总体百分比差异为32.6%（标准差=2.09），PD-MABs与PD-HABs之间为43.1%（标准差=1.21）。
未来需要进一步研究以确定[F]-FEPPA作为神经炎症生物标志物的意义，以及rs6971多态性在PD中的重要性及其临床后果。
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