Department of Geriatrics and Gerontology, Division of Brain Science, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan.
Department of Pharmacology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan.
Acta Neuropathol Commun. 2018 Jun 29;6(1):53. doi: 10.1186/s40478-018-0556-7.
Recent positron emission tomography (PET) studies have demonstrated the accumulation of tau PET tracer in the affected region of progressive supranuclear palsy (PSP) cases. To confirm the binding target of radiotracer in PSP, we performed an imaging-pathology correlation study in two autopsy-confirmed PSP patients who underwent [F]THK5351 PET before death. One patient with PSP Richardson syndrome showed elevated tracer retention in the globus pallidus and midbrain. In a patient with PSP-progressive nonfluent aphasia, [F]THK5351 retention also was observed in the cortical areas, particularly the temporal cortex. Neuropathological examination confirmed PSP in both patients. Regional [F]THK5351 standardized uptake value ratio (SUVR) in antemortem PET was significantly correlated with monoamine oxidase-B (MAO-B) level, reactive astrocytes density, and tau pathology at postmortem examination. In in vitro autoradiography, specific THK5351 binding was detected in the area of antemortem [F]THK5351 retention, and binding was blocked completely by a reversible selective MAO-B inhibitor, lazabemide, in brain samples from these patients. In conclusion, [F]THK5351 PET signals reflect MAO-B expressing reactive astrocytes, which may be associated with tau accumulation in PSP.
最近的正电子发射断层扫描（PET）研究表明，tau PET 示踪剂在进行性核上性麻痹（PSP）病例的受影响区域中积累。为了确认放射性示踪剂在 PSP 中的结合靶标，我们对两名在死亡前接受 [F]THK5351 PET 检查的尸检确诊 PSP 患者进行了成像-病理学相关性研究。一名 PSP Richardson 综合征患者的苍白球和中脑显示出放射性示踪剂保留升高。在一名 PSP-进行性非流利性失语症患者中，[F]THK5351 保留也在皮质区域，特别是颞叶皮质中观察到。神经病理学检查证实了两名患者均患有 PSP。在死亡前 PET 中，区域 [F]THK5351 标准化摄取值比（SUVR）与单胺氧化酶-B（MAO-B）水平、反应性星形胶质细胞密度和死后检查中的 tau 病理学显著相关。在体外放射自显影中，在生前 [F]THK5351 保留的区域中检测到特异性 THK5351 结合，并且在来自这些患者的脑样本中，结合被可逆选择性 MAO-B 抑制剂 lazabemide 完全阻断。总之，[F]THK5351 PET 信号反映了 MAO-B 表达的反应性星形胶质细胞，这可能与 PSP 中的 tau 积累有关。
