MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA, USA.
Department of Neurology, Massachusetts General Hospital, WACC Suite 715., 15th Parkman St., Boston, MA, 02114, USA.
Acta Neuropathol. 2017 Oct;134(4):619-628. doi: 10.1007/s00401-017-1740-8. Epub 2017 Jun 13.
[F-18]-AV-1451, a PET tracer specifically developed to detect brain neurofibrillary tau pathology, has the potential to facilitate accurate diagnosis of Alzheimer's disease (AD), staging of brain tau burden and monitoring disease progression. Recent PET studies show that patients with mild cognitive impairment and AD dementia exhibit significantly higher in vivo [F-18]-AV-1451 retention than cognitively normal controls. Importantly, PET patterns of [F-18]-AV-1451 correlate well with disease severity and seem to match the predicted topographic Braak staging of neurofibrillary tangles (NFTs) in AD, although this awaits confirmation. We studied the correlation of autoradiographic binding patterns of [F-18]-AV-1451 and the stereotypical spatiotemporal pattern of progression of NFTs using legacy postmortem brain samples representing different Braak NFT stages (I-VI). We performed [F-18]-AV-1451 phosphor-screen autoradiography and quantitative tau measurements (stereologically based NFT counts and biochemical analysis of tau pathology) in three brain regions (entorhinal cortex, superior temporal sulcus and visual cortex) in a total of 22 cases: low Braak (I-II, n = 6), intermediate Braak (III-IV, n = 7) and high Braak (V-VI, n = 9). Strong and selective [F-18]-AV-1451 binding was detected in all tangle-containing regions matching precisely the observed pattern of PHF-tau immunostaining across the different Braak stages. As expected, no signal was detected in the white matter or other non-tangle containing regions. Quantification of [F-18]-AV-1451 binding was very significantly correlated with the number of NFTs present in each brain region and with the total tau and phospho-tau content as reported by Western blot and ELISA. [F-18]-AV-1451 is a promising biomarker for in vivo quantification of brain tau burden in AD. Neuroimaging-pathologic studies conducted on postmortem material from individuals imaged while alive are now needed to confirm these observations.
[F-18]-AV-1451 是一种专门开发用于检测脑神经纤维缠结 tau 病理学的 PET 示踪剂，有可能促进阿尔茨海默病 (AD) 的准确诊断、脑 tau 负担的分期和疾病进展的监测。最近的 PET 研究表明，轻度认知障碍和 AD 痴呆患者的体内 [F-18]-AV-1451 保留明显高于认知正常对照组。重要的是，[F-18]-AV-1451 的 PET 模式与疾病严重程度密切相关，似乎与 AD 中神经原纤维缠结 (NFT) 的预测拓扑 Braak 分期相匹配，尽管这有待证实。我们使用代表不同 Braak NFT 阶段 (I-VI) 的遗留死后大脑样本研究了 [F-18]-AV-1451 的放射性自显影结合模式与 NFT 进行性的典型时空模式之间的相关性。我们在总共 22 例中进行了 [F-18]-AV-1451 磷屏放射自显影和 tau 定量测量（基于立体定向的 NFT 计数和 tau 病理学的生化分析）：低 Braak（I-II，n=6）、中 Braak（III-IV，n=7）和高 Braak（V-VI，n=9）。在所有含有缠结的区域中均检测到强烈且选择性的 [F-18]-AV-1451 结合，与不同 Braak 阶段 PHF-tau 免疫染色的观察模式完全匹配。正如预期的那样，在白质或其他不含缠结的区域未检测到信号。[F-18]-AV-1451 结合的定量与每个脑区中存在的 NFT 数量以及 Western blot 和 ELISA 报告的总 tau 和磷酸化 tau 含量非常显著相关。[F-18]-AV-1451 是 AD 中脑 tau 负担体内定量的有前途的生物标志物。现在需要对生前成像个体的死后材料进行神经影像学-病理学研究来证实这些观察结果。
