tau 和淀粉样蛋白 β 正电子发射断层扫描在额颞叶变性中的敏感性-特异性。
Sensitivity-Specificity of Tau and Amyloid β Positron Emission Tomography in Frontotemporal Lobar Degeneration.
机构信息
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Vita-Salute San Raffaele University, Milan, Italy.
出版信息
Ann Neurol. 2020 Nov;88(5):1009-1022. doi: 10.1002/ana.25893. Epub 2020 Sep 12.
OBJECTIVE
To examine associations between tau and amyloid β (Aβ) molecular positron emission tomography (PET) and both Alzheimer-related pathology and 4-repeat tau pathology in autopsy-confirmed frontotemporal lobar degeneration (FTLD).
METHODS
Twenty-four patients had [ F]-flortaucipir-PET and died with FTLD (progressive supranuclear palsy [PSP], n = 10; corticobasal degeneration [CBD], n = 10; FTLD-TDP, n = 3; and Pick disease, n = 1). All but 1 had Pittsburgh compound B (PiB)-PET. Braak staging, Aβ plaque and neurofibrillary tangle counts, and semiquantitative tau lesion scores were performed. Flortaucipir standard uptake value ratios (SUVRs) were calculated in a temporal meta region of interest (meta-ROI), entorhinal cortex and cortical/subcortical regions selected to match the tau lesion analysis. Global PiB SUVR was calculated. Autoradiography was performed in 1 PSP patient, with digital pathology used to quantify tau burden.
RESULTS
Nine cases (37.5%) had Aβ plaques. Global PiB SUVR correlated with Aβ plaque count, with 100% specificity and 50% sensitivity for diffuse plaques. Twenty-one (87.5%) had Braak stages I to IV. Flortaucipir correlated with neurofibrillary tangle counts in entorhinal cortex, but entorhinal and meta-ROI SUVRs were not elevated in Braak IV or primary age-related tauopathy. Flortaucipir uptake patterns differed across FTLD pathologies and could separate PSP and CBD. Flortaucipir correlated with tau lesion score in red nucleus and midbrain tegmentum across patients, but not in cortical or basal ganglia regions. Autoradiography demonstrated minimal uptake of flortaucipir, although flortaucipir correlated with quantitative tau burden across regions.
INTERPRETATION
Molecular PET shows expected correlations with Alzheimer-related pathology but lacks sensitivity to detect mild Alzheimer pathology in FTLD. Regional flortaucipir uptake was able to separate CBD and PSP. ANN NEUROL 2020;88:1009-1022.
目的
研究 tau 和淀粉样蛋白 β（Aβ）分子正电子发射断层扫描（PET）与经尸检证实的额颞叶变性（FTLD）中阿尔茨海默病相关病理学和 4 重复 tau 病理学之间的关联。
方法
24 例患者接受[F]-flortaucipir-PET 检查并死于 FTLD（进行性核上性麻痹[PSP]，n=10；皮质基底节变性[CBD]，n=10；FTLD-Tau 病，n=3；和 Pick 病，n=1）。除 1 例外，所有患者均接受了匹兹堡化合物 B（PiB）-PET 检查。进行 Braak 分期、Aβ斑块和神经原纤维缠结计数以及半定量 tau 病变评分。在颞叶感兴趣区（meta-ROI）中计算 flortaucipir 标准摄取值比值（SUVR），并选择与 tau 病变分析相匹配的内嗅皮层和皮质/皮质下区域计算 PiB 全局 SUVR。在 1 例 PSP 患者中进行了放射性自显影，使用数字病理学来量化 tau 负担。
结果
9 例（37.5%）有 Aβ斑块。全局 PiB SUVR 与 Aβ斑块计数相关，弥漫性斑块的特异性为 100%，敏感性为 50%。21 例（87.5%）患者处于 Braak 分期 I 至 IV 期。flortaucipir 与内嗅皮层神经原纤维缠结计数相关，但在 Braak IV 或原发性年龄相关 tau 病中，内嗅皮层和 meta-ROI SUVR 并未升高。flortaucipir 的摄取模式在不同的 FTLD 病理学中有所不同，可将 PSP 和 CBD 区分开来。flortaucipir 与患者的红核和中脑被盖区 tau 病变评分相关，但与皮质或基底节区域无关。放射性自显影显示 flortaucipir 的摄取量很少，但 flortaucipir 与跨区域的定量 tau 负担相关。
结论
分子 PET 与阿尔茨海默病相关病理学具有预期的相关性，但缺乏检测 FTLD 中轻度阿尔茨海默病病理的敏感性。区域性 flortaucipir 摄取能够将 CBD 和 PSP 区分开来。
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