Low neural exosomal levels of cellular survival factors in Alzheimer's disease.
Low neural exosomal levels of cellular survival factors in Alzheimer's disease.
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DOI：
10.1002/acn3.211
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发表时间：
2015-07
影响因子：
5.3
通讯作者：
Kapogiannis D
中科院分区：
文献类型：
--
作者：
Goetzl EJ;Boxer A;Schwartz JB;Abner EL;Petersen RC;Miller BL;Carlson OD;Mustapic M;Kapogiannis D
在阿尔茨海默病或额颞叶痴呆患者和匹配对照的血浆神经源性外泌体中，对介导神经元防御不同压力的转录因子进行了定量。阿尔茨海默病患者的外泌体中低密度脂蛋白受体相关蛋白 6、热休克因子 1 和阻遏元件 1 沉默转录因子的水平均显着低于对照组（P < 0.0001）。在额颞叶痴呆中，唯一显着的差异是阻遏元件 1 沉默转录因子的水平高于对照组。在临床诊断阿尔茨海默病之前 2-10 年，外泌体转录因子就减少了。外泌体中存活蛋白的低水平可能解释了神经元对阿尔茨海默病神经毒性蛋白的抵抗力下降。
Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer’s disease or frontotemporal dementia patients and matched controls. Exosomal levels of low-density lipoprotein receptor-related protein 6, heat-shock factor-1, and repressor element 1-silencing transcription factor all were significantly lower in Alzheimer’s disease patients than controls (P < 0.0001). In frontotemporal dementia, the only significant difference was higher levels of repressor element 1-silencing transcription factor than in controls. Exosomal transcription factors were diminished 2–10 years before clinical diagnosis of Alzheimer’s disease. Low exosomal levels of survival proteins may explain decreased neuronal resistance to Alzheimer’s disease neurotoxic proteins.