Departments of Neurology.
Department of Neuroscience, College of Medicine.
Alzheimer Dis Assoc Disord. 2018 Jan-Mar;32(1):62-69. doi: 10.1097/WAD.0000000000000216.
Semantic variant primary progressive aphasia (svPPA) has been associated with a variety of proteinopathies, mainly transactive response DNA-binding protein, but also with tau and β-amyloid. Recently selective tau tracers for positron emission tomography (PET) have been developed to determine the presence of cerebral tau deposits in vivo. Here, we investigated the topographical distribution of THK5351 in svPPA patients.
Five svPPA patients, 14 Alzheimer's disease patients, and 15 age-matched normal controls underwent [F]-THK5351 PET scans, magnetic resonance imaging, and detailed neuropsychological tests. [F]-fluorodeoxyglucose PET was obtained in 3 svPPA patients, whereas the remaining 2 underwent amyloid PET using [F]-flutemetamol. Tau distribution among the 3 groups was compared using regions of interest-based and voxel-based statistical analyses.
In svPPA patients, [F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared with the normal controls group (left>right), and in the left inferior and temporal polar region compared with Alzheimer's disease patients. [F]-THK5351 retention inversely correlated with glucose metabolism, whereas regional THK retention correlated with clinical severity. [F]-flutemetamol scans were negative for β-amyloid.
These findings show that [F]-THK5351 retention may be detected in cortical regions correlating with svPPA pathology.
语义变异原发性进行性失语症（svPPA）与多种蛋白病有关，主要是反式作用反应 DNA 结合蛋白，但也与tau 和 β-淀粉样蛋白有关。最近，开发了用于正电子发射断层扫描（PET）的选择性 tau 示踪剂，以确定脑内 tau 沉积物的存在。在这里，我们研究了 THK5351 在 svPPA 患者中的分布情况。
5 名 svPPA 患者、14 名阿尔茨海默病患者和 15 名年龄匹配的正常对照者接受了[F]-THK5351 PET 扫描、磁共振成像和详细的神经心理学测试。3 名 svPPA 患者获得了[F]-氟脱氧葡萄糖 PET，而其余 2 名患者则进行了[F]-flutemetamol 的淀粉样蛋白 PET。使用基于感兴趣区域和基于体素的统计分析比较了 3 组之间的 tau 分布。
在 svPPA 患者中，与正常对照组相比，[F]-THK5351 在前后颞叶皮质（左侧>右侧）和左侧颞极区的保留增加，与阿尔茨海默病患者相比。[F]-THK5351 保留与葡萄糖代谢呈负相关，而区域 THK 保留与临床严重程度相关。[F]-flutemetamol 扫描对β-淀粉样蛋白呈阴性。
这些发现表明，在与 svPPA 病理学相关的皮质区域可能检测到[F]-THK5351 的保留。
