Mak Elijah, Kouli Antonina, Holland Negin, Nicastro Nicolas, Savulich George, Surendranathan Ajenthan, Malpetti Maura, Manavaki Roido, Hong Young T, Fryer Tim D, Aigbirhio Franklin, Rowe James B, O'Brien John T, Williams-Gray Caroline H
Department of Psychiatry, University of Cambridge, Cambridge CB22QQ, UK.
Department of Clinical Neurosciences and Cambridge University Hospital NHS Trust, University of Cambridge, Cambridge CB20SZ, UK.
Brain Commun. 2021 Aug 28;3(3):fcab177. doi: 10.1093/braincomms/fcab177. eCollection 2021.
While [F]-AV-1451 was developed as a PET radiotracer with high affinity for hyperphosphorylated tau, it has been proposed that loss of 'off-target' [F]-AV-1451 binding to neuromelanin in the substantia nigra could be a surrogate marker of Lewy body diseases. [F]-AV-1451 binding was measured in the substantia nigra of patients with Parkinson's disease ( = 35), dementia with Lewy bodies ( = 10) and separate control groups ( = 37; = 14). Associations with motor symptoms, cognition and disease duration were evaluated using linear regression models. The dementia with Lewy bodies group had significantly reduced substantia nigra [F]-AV-1451 binding compared to controls after adjusting for age ( < 0.05). However, there were no significant differences in substantia nigra [F]-AV-1451 binding between Parkinson's disease and controls. Substantia nigra [F]-AV-1451 binding was not associated with age, disease duration, Movement Disorders Society-Unified Parkinson's Disease Rating Scale and cognitive scores in dementia with Lewy bodies and Parkinson's disease groups. Despite the reduction of substantia nigra [F]-AV-1451 binding in dementia with Lewy bodies, these findings suggest that substantia nigra [F]-AV-1451 binding has no value as a diagnostic marker in early Parkinson's disease. Further investigations in longitudinal cohorts are warranted.
虽然[F]-AV-1451是作为一种对过度磷酸化tau具有高亲和力的正电子发射断层扫描（PET）放射性示踪剂而开发的，但有人提出，“脱靶”的[F]-AV-1451与黑质中神经黑色素结合的丧失可能是路易体疾病的替代标志物。在帕金森病患者（n = 35）、路易体痴呆患者（n = 10）和单独的对照组（n = 37；n = 14）的黑质中测量了[F]-AV-1451的结合情况。使用线性回归模型评估了与运动症状、认知和疾病持续时间的相关性。在调整年龄后，路易体痴呆组的黑质[F]-AV-1451结合与对照组相比显著降低（P < 0.05）。然而，帕金森病组和对照组之间的黑质[F]-AV-1451结合没有显著差异。在路易体痴呆和帕金森病组中，黑质[F]-AV-1451结合与年龄、疾病持续时间、运动障碍协会统一帕金森病评定量表和认知评分均无关联。尽管路易体痴呆患者黑质中[F]-AV-1451结合减少，但这些发现表明黑质[F]-AV-1451结合在早期帕金森病中作为诊断标志物没有价值。有必要在纵向队列中进行进一步研究。
