一个来自大脑的tau寡合物多态体与对阿尔茨海默病的认知性有关
Michela Marcatti1, Batbayar Tumurbaatar1, Wen Ru Zhang1
1Mitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
概括
患有阿尔茨海默氏症病理但没有痴呆症的个体具有明显的,稳定的tau多态. 这些无毒的寡合体可能解释认知性,并提供新的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
背景情况:
- 错误折叠的陶蛋白形成不同的多态,影响阿尔茨海默病 (AD) 的进展.
- 一些患有阿尔茨海默氏症病理的个体在认知上保持完整 (与阿尔茨海默氏症神经病理学 (NDAN) 无痴呆),这表明了独特的tau多态特征.
研究的目的:
- 调查和比较来自AD和NDAN个体的大脑衍生的寡合体 (BDTOs) 的特性.
- 探索TAU多态结构与AD病理存在的认知弹性之间的潜在联系.
主要方法:
- 从AD和NDAN个体的死后海马中分离BDTOs.
- 通过蛋白酶消化,免疫特征,AFM,tau播种试验,电生理学和毒性试验,评估BDTOs的生物物理,生物化学和功能性质.
主要成果:
- 与AD-BDTO相比,NDAN-BDTO表现出更大的蛋白质酶耐药性,明显的形状特征,并形成更大的聚合物.
- 与AD-BDTO相比,NDAN-BDTOs保留了突触功能,并且表现出较低的神经元毒性.
- 虽然两种BDTO类型都产生了tau聚合的种子,但NDAN-BDTOs产生了毒性较低的组件.
结论:
- 在NDAN个体中,结构稳定,毒性较小的tau多态可能是认知性的基础.
- 针对特定的,无毒的多态体,为阿尔茨海默病提供了潜在的治疗策略.
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