阿尔茨海默病人脑组织细胞外囊泡的蛋白质组学和生物学特征分析。
Proteomic and biological profiling of extracellular vesicles from Alzheimer's disease human brain tissues.
机构信息
Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA.
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts, USA.
出版信息
Alzheimers Dement. 2020 Jun;16(6):896-907. doi: 10.1002/alz.12089. Epub 2020 Apr 17.
INTRODUCTION
Extracellular vesicles (EVs) from human Alzheimer's disease (AD) biospecimens contain amyloid beta (Aβ) peptide and tau. While AD EVs are known to affect brain disease pathobiology, their biochemical and molecular characterizations remain ill defined.
METHODS
EVs were isolated from the cortical gray matter of 20 AD and 18 control brains. Tau and Aβ levels were measured by immunoassay. Differentially expressed EV proteins were assessed by quantitative proteomics and machine learning.
RESULTS
Levels of pS396 tau and Aβ1-42 were significantly elevated in AD EVs. High levels of neuron- and glia-specific factors are detected in control and AD EVs, respectively. Machine learning identified ANXA5, VGF, GPM6A, and ACTZ in AD EV compared to controls. They distinguished AD EVs from controls in the test sets with 88% accuracy.
DISCUSSION
In addition to Aβ and tau, ANXA5, VGF, GPM6A, and ACTZ are new signature proteins in AD EVs.
简介
来自人类阿尔茨海默病（AD）生物样本的细胞外囊泡（EVs）含有淀粉样β（Aβ）肽和 tau。虽然 AD EVs 已知会影响大脑疾病的病理生物学，但它们的生化和分子特征仍未得到明确界定。
方法
从 20 例 AD 和 18 例对照大脑的皮质灰质中分离 EVs。通过免疫测定法测量 tau 和 Aβ 水平。通过定量蛋白质组学和机器学习评估差异表达的 EV 蛋白。
结果
AD EVs 中 pS396 tau 和 Aβ1-42 的水平显著升高。在对照和 AD EVs 中分别检测到神经元和神经胶质特异性因子的高水平。与对照相比，机器学习在 AD EV 中鉴定到 ANXA5、VGF、GPM6A 和 ACTZ。它们以 88%的准确率在测试集中区分 AD EV 和对照。
讨论
除了 Aβ 和 tau，ANXA5、VGF、GPM6A 和 ACTZ 是 AD EV 中的新特征蛋白。
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