Tauopathies are neurodegenerative diseases characterized by tau inclusions in brain cells. Seed-competent tau species have been suggested to spread from cell to cell in a stereotypical manner, indicating that this may involve a prion-like mechanism. Although the intercellular mechanisms of transfer are unclear, extracellular vesicles (EVs) could be potential shuttles. We assessed this in humans by preparing vesicles from fluids (brain-derived enriched EVs [BD-EVs]). These latter were isolated from different brain regions in various tauopathies, and their seeding potential was assessed in vitro and in vivo. We observed considerable heterogeneity among tauopathies and brain regions. The most striking evidence was coming mainly from Alzheimer’s disease where the BD-EVs clearly contain pathological species that can induce tau lesions in vivo. The results support the hypothesis that BD-EVs participate in the prion-like propagation of tau pathology among tauopathies, and there may be implications for diagnostic and therapeutic strategies.

Tau 病是以脑细胞中的 tau 包涵体为特征的神经退行性疾病。有种子能力的 tau 物种被认为以一种刻板的方式从一个细胞传播到另一个细胞，表明这可能涉及一种类似朊病毒的机制。尽管转移的细胞间机制尚不清楚，但细胞外囊泡 (EV) 可能是潜在的穿梭机。我们通过从液体中制备囊泡（脑源性富集 EV [BD-EV]）来评估这一点。后者是从各种 tau 病的不同脑区分离出来的，并在体外和体内评估了它们的播种潜力. 我们观察到 tau 病变和大脑区域之间存在相当大的异质性。最引人注目的证据主要来自阿尔茨海默病，其中 BD-EV 明显含有可在体内诱发 tau 病变的病理物种。结果支持 BD-EV 参与 tau 病变中 tau 病理学的朊病毒样传播的假设，并且可能对诊断和治疗策略有影响。