近日，爱丁堡大学的英国痴呆症研究所教授Tara L. Spires-Jones及其小组开发出人类进行性核上性麻痹中低聚tau蛋白跨突触传播的证据。该项研究成果发表在2025年7月16日出版的《自然—神经科学》上。

研究人员测试了病理性tau有助于突触丢失的假设，并可能通过从突触前转移到突触后在大脑中传播。使用死后PSP脑样本和活体人脑切片培养模型，该研究组观察到突触对中的病理tau，并证明低聚tau可以进入活体人脑突触后。蛋白质组学结果显示，PSP突触中织丝蛋白增加，超分辨率成像显示织丝蛋白与tau蛋白在突触中的共定位距离足够近，可以成为tau蛋白的结合伙伴，这可能介导了tau蛋白的传播。突触中tau蛋白的积累与突触丢失相关，并且观察到星形胶质细胞对突触的吞噬，提示星形胶质细胞参与突触丢失。总之，这些数据表明，靶向突触tau是治疗PSP的一种有希望的方法。

研究人员表示，在神经退行性疾病进行性核上性麻痹（PSP）中，tau病理以一种典型的时空模式在大脑中发展，tau病理出现的地方突触丢失。

附：英文原文

Title: Evidence for trans-synaptic propagation of oligomeric tau in human progressive supranuclear palsy

Author: McGeachan, Robert I., Keavey, Lois, Simzer, Elizabeth M., Chang, Ya Yin, Rose, Jamie L., Spires-Jones, Maxwell P., Gilmore, Mollie, Holt, Kristjan, Meftah, Soraya, Ravingerova, Natalia, Scutariu, Cristina, Taylor, Lewis W., King, Declan, Tzioras, Makis, Tulloch, Jane, Booker, Sam A., Liaquat, Imran, Hindley-Pollock, Nicole, Geary, Bethany, Smith, Colin, Brennan, Paul M., Durrant, Claire S., Spires-Jones, Tara L.

Issue&Volume: 2025-07-16

Abstract: In the neurodegenerative disease progressive supranuclear palsy (PSP), tau pathology progresses through the brain in a stereotypical spatiotemporal pattern, and where tau pathology appears, synapses are lost. We tested the hypothesis that pathological tau contributes to synapse loss and may spread through the brain by moving from presynapses to postsynapses. Using postmortem PSP brain samples and a living human brain slice culture model, we observe pathological tau in synaptic pairs and evidence that oligomeric tau can enter live human postsynapses. Proteomics revealed increased clusterin in synapses in PSP, and super-resolution imaging showed clusterin colocalized with tau in synapses in close enough proximity to be binding partners, which may mediate tau spread. Accumulation of tau in synapses correlated with synapse loss, and synaptic engulfment by astrocytes was observed, suggesting that astrocytes contribute to synapse loss. Together, these data indicate that targeting synaptic tau is a promising approach to treat PSP.

DOI: 10.1038/s41593-025-01992-5

Source: https://www.nature.com/articles/s41593-025-01992-5