Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland and Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland.
Unit of ClinicalNeuroscience, Neurosurgery, University of Oulu and Medical Research Center, Oulu University Hospital, Oulu, Finland.
J Alzheimers Dis. 2018;64(1):171-179. doi: 10.3233/JAD-180071.
Detection of pathological tau aggregates could facilitate clinical diagnosis of Alzheimer's disease (AD) and monitor drug effects in clinical trials. S-[18F]THK-5117 could be a potential tracer to detect pathological tau deposits in brain. However, no previous study have correlated S-[18F]THK-5117 uptake in PET with brain biopsy verified tau pathology in vivo.
Here we aim to evaluate the association between cerebrospinal fluid (CSF) AD biomarkers, S-[18F]THK-5117, and [11C]PIB PET against tau and amyloid lesions in brain biopsy.
Fourteen patients with idiopathic normal pressure hydrocephalus (iNPH) with previous shunt surgery including right frontal cortical brain biopsy and CSF Aβ1 - 42, total tau, and P-tau181 measures, underwent brain MRI, [11C]PIB PET, and S-[18F]THK-5117 PET imaging.
Seven patients had amyloid-β (Aβ, 4G8) plaques, two both Aβ and phosphorylated tau (Pτ, AT8) and one only Pτ in biopsy. As expected, increased brain biopsy Aβ was well associated with higher [11C]PIB uptake in PET. However, S-[18F]THK-5117 uptake did not show any statistically significant correlation with either brain biopsy Pτ or CSF P-tau181 or total tau.
S-[18F]THK-5117 lacked clear association with neuropathologically verified tau pathology in brain biopsy probably, at least partially, due to off-target binding. Further studies with larger samples of patients with different tau tracers are urgently needed. The detection of simultaneous Aβ and tau pathology in iNPH is important since that may indicate poorer and especially shorter response for CSF shunt surgery compared with no pathology.
病理性 tau 聚集物的检测有助于阿尔茨海默病（AD）的临床诊断，并在临床试验中监测药物的疗效。S-[18F]THK-5117 可能是一种潜在的示踪剂，可用于检测大脑中的病理性 tau 沉积物。然而，以前没有研究将 PET 中的 S-[18F]THK-5117 摄取与体内经脑活检证实的 tau 病理学相关联。
本研究旨在评估脑脊髓液（CSF）AD 生物标志物、S-[18F]THK-5117 和[11C]PIB PET 与脑活检 tau 和淀粉样蛋白病变之间的相关性。
14 例特发性正常压力脑积水（iNPH）患者曾接受过分流手术，包括右额皮质脑活检和 CSF Aβ1-42、总 tau 和 P-tau181 检测，进行脑 MRI、[11C]PIB PET 和 S-[18F]THK-5117 PET 成像。
7 例患者有淀粉样蛋白-β（Aβ，4G8）斑块，2 例既有 Aβ又有磷酸化 tau（Pτ，AT8），1 例只有 Pτ。正如预期的那样，脑活检中 Aβ 增加与 [11C]PIB 在 PET 中的摄取量增加呈正相关。然而，S-[18F]THK-5117 摄取量与脑活检 Pτ或 CSF P-tau181 或总 tau 均无统计学意义的相关性。
S-[18F]THK-5117 与脑活检中经病理证实的 tau 病理学缺乏明确的相关性，可能至少部分原因是由于脱靶结合。需要进一步研究，采用不同的 tau 示踪剂，增加患者样本量。在 iNPH 中同时检测 Aβ 和 tau 病理学非常重要，因为与无病理学相比，这可能表明 CSF 分流手术的反应较差，尤其是较短。
