体内 [18F]Flortaucipir 与死后阿尔茨海默病 Tau 病理学的相关性。
Correlation of In Vivo [18F]Flortaucipir With Postmortem Alzheimer Disease Tau Pathology.
机构信息
Department of Neurology, Skåne University Hospital, Lund, Sweden.
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
出版信息
JAMA Neurol. 2019 Mar 1;76(3):310-317. doi: 10.1001/jamaneurol.2018.3692.
IMPORTANCE
In Alzheimer disease (AD), tau filaments form neuronal inclusions in neurites (neuropil threads) and in somata (neurofibrillary tangles), and neurite tau pathology constitutes the most common pathology. Positron emission tomography (PET) ligands have been developed to detect in vivo tau pathology in AD. However, the association of AD tau pathology post mortem with in vivo tau PET retention has not been established. Therefore, there is a need to investigate the associations of tau PET with postmortem tau pathology in AD.
OBJECTIVE
To study the association of regional in vivo retention of the tau PET ligand [18F]flortaucipir (previously known as AV1451) with the density of tau neuropathology in the corresponding brain regions in a patient with AD.
DESIGN, SETTING, AND PARTICIPANTS: The patient was a man in his 40s with AD caused by a PSEN1 mutation. Between May 2015 and December 2016, he underwent 2 [18F]flortaucipir PET scans at Lund University Hospital, Lund, Sweden. Postmortem analysis was performed 12 months after the last PET scan. Tau pathology was assessed using phosphorylated tau (AT8) immunohistochemistry and Gallyas silver staining. In addition to the regional total tau pathology burden, the density of tau-positive neurites and intrasomal tau tangles were quantified using a stereology-based method. Further, β-amyloid-containing plaques were detected using 4G8 immunohistochemistry. Data were analyzed between January 2018 and August 2018.
MAIN OUTCOMES AND MEASURES
Regional standardized uptake value ratios of [18F]flortaucipir were compared with the amount of tau pathology in the corresponding brain areas.
RESULTS
In this patient, the clinical disease symptoms progressed rapidly in life, paralleled with an annual increase of tau PET retention of 20% to 40% in many cortical regions. Compared with postmortem immunohistochemistry, regional in vivo uptake of [18F]flortaucipir was correlated with the density of tau-positive neurites (AT8: rs = 0.87; P < .001; Gallyas: rs = 0.92; P < .001), intrasomal tau tangles (AT8: rs = 0.65; P = .01; Gallyas: rs = 0.84; P < .001), and total tau burden (AT8: rs = 0.84; P < .001; Gallyas: rs = 0.82; P < .001). No correlations between [18F]flortaucipir and β-amyloid pathology were found.
CONCLUSIONS AND RELEVANCE
These results indicate that [18F]flortaucipir PET retention is a robust in vivo measure of the total AD tau burden.
重要性
在阿尔茨海默病（AD）中，tau 丝形成神经元突起内的神经元内含物（神经原纤维丝）和胞体内（神经纤维缠结），并且神经突 tau 病理学构成最常见的病理学。已经开发了正电子发射断层扫描（PET）配体来在 AD 中体内检测 tau 病理学。然而，AD 死后 tau 病理学与体内 tau PET 保留之间的关联尚未建立。因此，需要研究 tau PET 与 AD 中死后 tau 病理学的关联。
目的
研究 tau PET 配体[18F]flortaucipir（以前称为 AV1451）在体内的区域保留与 AD 患者相应脑区 tau 神经病理学密度之间的关系。
设计、地点和参与者：患者是一名 40 多岁的男性，因 PSEN1 突变导致 AD。2015 年 5 月至 2016 年 12 月，他在瑞典隆德大学医院接受了 2 次[18F]flortaucipir PET 扫描。死后分析是在最后一次 PET 扫描后 12 个月进行的。使用磷酸化 tau（AT8）免疫组织化学和 Gallyas 银染色来评估 tau 病理学。除了区域总 tau 病理学负担外，还使用基于立体学的方法来定量 tau 阳性神经突和细胞内 tau 缠结的密度。进一步使用 4G8 免疫组织化学检测β-淀粉样蛋白含量斑块。数据在 2018 年 1 月至 2018 年 8 月之间进行了分析。
主要结果和测量
将[18F]flortaucipir 的区域标准化摄取值比与相应脑区的 tau 病理学量进行比较。
结果
在这名患者中，临床疾病症状在生命中迅速进展，与皮质区域中 tau PET 保留的每年 20%至 40%的增加相平行。与死后免疫组织化学相比，[18F]flortaucipir 的区域体内摄取与 tau 阳性神经突（AT8：rs = 0.87；P <.001；Gallyas：rs = 0.92；P <.001）、细胞内 tau 缠结（AT8：rs = 0.65；P =.01；Gallyas：rs = 0.84；P <.001）和总 tau 负担（AT8：rs = 0.84；P <.001；Gallyas：rs = 0.82；P <.001）相关。未发现[18F]flortaucipir 和 β-淀粉样蛋白病理学之间存在相关性。
结论和相关性
这些结果表明，[18F]flortaucipir PET 保留是 AD 总 tau 负担的可靠体内测量指标。
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