Suzuki Hisaomi, Kubota Manabu, Kurose Shin, Tagai Kenji, Endo Hironobu, Onaya Mitsumoto, Yamamoto Yasuharu, Sahara Naruhiko, Ohgidani Masahiro, Haga Chie, Hara Hiroya, Akiyama Haruhiko, Takahata Keisuke, Higuchi Makoto
Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, 4- 9-1 Anagawa, Inage, Chiba, 263-8555, Japan.
Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan.
EJNMMI Res. 2025 Jul 31;15(1):96. doi: 10.1186/s13550-025-01296-6.
Pick's disease (PiD) is classified as frontotemporal lobar degeneration with pathological tau aggregates. Positron emission tomography (PET) with F-florzolotau provides high-contrast imaging of diverse tau fibrils. While our previous work demonstrated the detectability of three repeat (3R) tau pathology by F-florzolotau PET in an autopsy-confirmed PiD patient, its potential for quantitative assessment of 3R tau aggregates in living individuals remains unclear. In this study, we analyzed correlations between in vivo F-florzolotau retentions and postmortem neuropathological data across brain regions in the same case with PiD.
The patient was 60 years of age at the time of death and had been diagnosed with behavioral variant frontotemporal dementia. The patient underwent F-florzolotau PET one year prior to death and was given the pathological diagnosis of PiD by brain autopsy. Regional tau pathology was assessed using Bodian's silver staining and immunohistochemistry with a monoclonal antibody (AT8). Histopathological assays revealed abundant intraneuronal Pick bodies along with neuropil threads in frontotemporal and other brain areas. In the cerebral cortex, AT8-positive areas exhibited a significant positive correlation with F-florzolotau binding in the corresponding regions (Pearson's r = 0.81, p < 0.001) estimated as standardized uptake value ratio corrected for partial volume effect. In contrast, no such associations were found in subcortical structures. Furthermore, a substantial proportion of Pick bodies displayed fluorescence co-labelled with florzolotau and AT8 antibodies.
Collectively, the present findings support the capability of F-florzolotau PET for the in vivo quantification of 3R tau fibrils.
皮克病（PiD）被归类为伴有病理性tau蛋白聚集体的额颞叶变性。使用F-florzolotau进行正电子发射断层扫描（PET）可对多种tau原纤维进行高对比度成像。虽然我们之前的研究表明，在尸检确诊的PiD患者中，F-florzolotau PET能够检测到三重复（3R）tau蛋白病变，但其在活体个体中对3R tau蛋白聚集体进行定量评估的潜力仍不清楚。在本研究中，我们分析了同一例PiD患者脑内F-florzolotau滞留与死后神经病理学数据在各脑区之间的相关性。
患者死亡时60岁，被诊断为行为变异型额颞叶痴呆。患者在死亡前一年接受了F-florzolotau PET检查，并通过脑尸检获得了PiD的病理诊断。使用博迪安银染色和单克隆抗体（AT8）免疫组织化学评估区域tau蛋白病变。组织病理学检测显示，额颞叶和其他脑区有丰富的神经元内皮克小体以及神经毡丝。在大脑皮层，AT8阳性区域与相应区域的F-florzolotau结合呈显著正相关（Pearson相关系数r = 0.81，p < 0.001），以校正部分容积效应的标准化摄取值比估算。相比之下，在皮质下结构中未发现此类关联。此外，相当一部分皮克小体显示出与florzolotau和AT8抗体共标记的荧光。
总体而言，本研究结果支持F-florzolotau PET在体内定量3R tau原纤维的能力。
