The protein tau, when misfolded in neurodegenerative diseases, has several prion-like properties including being able to spread by cell-to-cell transfer, induce templated seeding, and exist in distinct conformational strains. These properties of transmission may present health hazards when lesion-containing biospecimens are used in research and neuropathology laboratories. We evaluated the impact standard sterilization and cleaning methods have on the capacity of tau seeds to induce aggregation. We employed a previously developed, highly sensitive FRET-based biosensor assay to assess remnant tau seeding after exposure to these procedures. For tau species derived from human Alzheimer disease tissue (brain homogenate and sarkosyl-insoluble fibrils), both autoclaving and incubation in 90.6% formic acid were sufficient to reduce tau bioactivity. By contrast, boiling was not always effective in completely blocking bioactivity in the seeding assay. Notably, only formic acid incubation was able to produce a similar reduction in tissue from a P301L mutant tau mouse model of tauopathy. Our study highlights nuances in methods for inactivation of tau seeding which may support adapted tissue processing procedures, especially in research settings. These findings also highlight the importance of universal precautions when handling human neuropathological and research laboratory materials.

中文翻译：

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灭菌方法对人类 Tau 蛋白种子播种能力的影响

tau 蛋白在神经退行性疾病中错误折叠时，具有多种类似朊病毒的特性，包括能够通过细胞间转移进行传播、诱导模板化播种以及存在于不同的构象菌株中。当在研究和神经病理学实验室中使用含有病变的生物样本时，这些传播特性可能会对健康造成危害。我们评估了标准灭菌和清洁方法对 tau 种子诱导聚集能力的影响。我们采用以前开发的、基于 FRET 的高灵敏度生物传感器测定法来评估暴露于这些程序后的残余 tau 播种。对于源自人类阿尔茨海默病组织的 tau 物种（脑匀浆和不溶于肌氨酸的原纤维），高压灭菌和在 90.6% 甲酸中孵育都足以降低 tau 生物活性。相比之下，煮沸并不总是有效地完全阻断接种试验中的生物活性。值得注意的是，只有甲酸孵育能够从 tau 病变的 P301L 突变 tau 小鼠模型中产生类似的组织减少。我们的研究强调了 tau 播种失活方法的细微差别，这可能支持适应的组织处理程序，特别是在研究环境中。这些发现还强调了在处理人类神经病理学和研究实验室材料时采取普遍预防措施的重要性。我们的研究强调了 tau 播种失活方法的细微差别，这可能支持适应的组织处理程序，特别是在研究环境中。这些发现还强调了在处理人类神经病理学和研究实验室材料时采取普遍预防措施的重要性。我们的研究强调了 tau 播种失活方法的细微差别，这可能支持适应的组织处理程序，特别是在研究环境中。这些发现还强调了在处理人类神经病理学和研究实验室材料时采取普遍预防措施的重要性。