[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是专为检测脑神经原纤维tau病理而开发的PET示踪剂，具有促进阿尔茨海默氏病（AD）准确诊断，脑tau负担分期和监测疾病进展的潜力。最近的PET研究表明，轻度认知障碍和AD痴呆症患者的体内[F-18] -AV-1451保留率明显高于认知正常对照。重要的是，[F-18] -AV-1451的PET模式与疾病严重程度密切相关，并且似乎与AD中神经原纤维缠结（NFT）的预测地形Braak分期相符，尽管这尚待证实。我们使用代表不同Braak NFT阶段（I-VI）的传统验尸脑样本研究了[F-18] -AV-1451的放射自显影结合模式与NFT进展的刻板时空模式的相关性。我们在总共三个脑区域（肠内皮层，颞上沟和视皮层）中进行了[F-18] -AV-1451磷光幕放射自显影和定量tau测量（基于病理学的NFT计数和tau病理的生化分析）。 22例：低位Braak（I–II，n  = 6），中级Braak（III–IV，n  = 7）和高Braak（V–VI，n = 9）。在所有包含缠结的区域中检测到强且选择性的[F-18] -AV-1451结合，这些区域与在不同Braak阶段中观察到的PHF-tau免疫染色模式精确匹配。如预期的那样，在白质或其他非缠结区域中未检测到信号。[F-18] -AV-1451结合的定量与每个大脑区域中存在的NFT数量以及总tau和磷酸化tau含量非常相关，如Western blot和ELISA报道。[F-18] -AV-1451是一种有前途的生物标志物，可用于AD中脑内tau负担的体内定量。现在需要对活着成像的个体的尸体材料进行神经影像病理学研究，以确认这些观察结果。