Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease
Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease
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DOI：
10.1212/wnl.0000000000001702
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发表时间：
2015-07-07
期刊：
影响因子：
9.9
通讯作者：
Kapogiannis, Dimitrios
中科院分区：
文献类型：
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作者：
Goetzl, Edward J.;Boxer, Adam;Kapogiannis, Dimitrios
目的：对阿尔茨海默病 (AD) 患者和对照患者的神经源性血液外泌体中的多种自体溶酶体蛋白进行定量，以研究紊乱的神经元自噬。方法：从 AD 患者 (n = 26) 或额颞叶痴呆 (n = 16) 以及其他 AD 患者 (n = 20) 中获得的血液外泌体在认知正常时和 1 至 10 年后诊断时进行丰富，并丰富病例对照神经源通过抗人L1CAM抗体免疫吸收。通过 ELISA 对提取的外泌体蛋白进行定量，并使用 CD81 外泌体标记物进行标准化。结果：在横断面研究中，与对照组相比，AD 组组织蛋白酶 D、溶酶体相关膜蛋白 1 (LAMP-1) 和泛素化蛋白的平均外泌体水平显着升高，热休克蛋白 70 显着降低 (p
Objective:Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy.Methods:Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients with AD (n = 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker.Results:Mean exosomal levels of cathepsin D, lysosome-associated membrane protein 1 (LAMP-1), and ubiquitinylated proteins were significantly higher and of heat-shock protein 70 significantly lower for AD than controls in cross-sectional studies (p