Fibril-type aggregates of tau occur in Alzheimer’s disease (AD) and dozens of tauopathies. Fibrils catalyze aggregation by prion-like seeding, which in part underlies disease progression. Seeding by recombinant and brain-derived tau fibrils is measured using biosensor cells that express aggregation-prone tau mutants fused with fluorescent reporter proteins. Seeding results in a punctated phenotype that is well established, but evidence that fluorescent tau fusion proteins from biosensor cells assemble into fibril-type structures is lacking. We investigated the effects of seeding on fibril formation by biosensor cells. Fluorescent punctated cell phenotypes that were catalyzed persisted with varying stabilities. Seeded cells bearing punctated phenotypes yielded sarkosyl-insoluble fibrils, although non-seeded cells did not. ImmunoEM of cell-purified fibrils shows that GFP localizes to the proteolytically sensitive fuzzy coat of tau fibrils. The presented data offer compelling evidence that fluorescent puncta are fibril-type aggregates of tau that result from prion-like seeding.

中文翻译：

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Tau 种子催化来自 GFP tau 生物传感器细胞的原纤维型结构


tau 的原纤维型聚集体发生在阿尔茨海默病 （AD） 和数十种 tau 蛋白病中。原纤维通过朊病毒样种子催化聚集，这在一定程度上是疾病进展的基础。使用生物传感器细胞测量重组和脑来源的 tau 原纤维的接种，这些细胞表达与荧光报告蛋白融合的易聚集 tau 突变体。接种产生已确立的点状表型，但缺乏来自生物传感器细胞的荧光 tau 融合蛋白组装成原纤维型结构的证据。我们研究了接种对生物传感器细胞形成原纤维的影响。被催化的荧光点状细胞表型以不同的稳定性持续存在。带有点状表型的接种细胞产生 sarkosyl 不溶性原纤维，但未接种的细胞没有。细胞纯化原纤维的免疫电镜显示 GFP 定位于 tau 原纤维的蛋白水解敏感的模糊涂层。提供的数据提供了令人信服的证据，证明荧光点是 tau 的原纤维型聚集体，由朊病毒样种子产生。