Global quantitative analysis of the human brain proteome and phosphoproteome in Alzheimer's disease.
Global quantitative analysis of the human brain proteome and phosphoproteome in Alzheimer's disease.
复制标题
DOI：
10.1038/s41597-020-00650-8
复制
发表时间：
2020-09-28
期刊：
影响因子：
9.8
通讯作者：
Seyfried NT
中科院分区：
文献类型：
--
作者：
Ping L;Kundinger SR;Duong DM;Yin L;Gearing M;Lah JJ;Levey AI;Seyfried NT
阿尔茨海默病（AD）的特征在于早期无症状阶段（AsymAD），其中个体在没有临床可检测到的认知下降的情况下表现出淀粉样蛋白β（Aβ）斑块积聚。在这里，我们报告了一个公正的多重定量蛋白质组学和磷酸化蛋白质组学分析使用串联质量标签（TMT）同量异序标记的人死后皮层（n = 27）在无病理对照，AsymAD和症状性AD的个人。利用离线高pH分级分离和液相色谱法，在Orbitrap Lumos质谱仪上耦合串联质谱法（LC-MS/MS），我们在三个TMT 11-plex批次中鉴定了11，378个蛋白质组。用固定化金属亲和层析（IMAC）富集来自相同TMT标记病例的磷酸肽，鉴定了51，736个磷酸肽。其中，48，992个通过代表33，652个独特磷酸位点的TMT报告离子定量。每个TMT 11-plex中包括两个参比标准品，以评估蛋白质和肽水平的批内和批间差异。这个全面的人脑蛋白质组和磷酸化蛋白质组数据集将作为一个有价值的资源，用于识别AD进展过程中改变的生化，细胞和信号通路。描述报告数据的机器可访问元数据文件：10.6084/m9.figshare.12901817
Alzheimer’s disease (AD) is characterized by an early, asymptomatic phase (AsymAD) in which individuals exhibit amyloid-beta (Aβ) plaque accumulation in the absence of clinically detectable cognitive decline. Here we report an unbiased multiplex quantitative proteomic and phosphoproteomic analysis using tandem mass tag (TMT) isobaric labeling of human post-mortem cortex (n = 27) across pathology-free controls, AsymAD and symptomatic AD individuals. With off-line high-pH fractionation and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) on an Orbitrap Lumos mass spectrometer, we identified 11,378 protein groups across three TMT 11-plex batches. Immobilized metal affinity chromatography (IMAC) was used to enrich for phosphopeptides from the same TMT-labeled cases and 51,736 phosphopeptides were identified. Of these, 48,992 were quantified by TMT reporter ions representing 33,652 unique phosphosites. Two reference standards in each TMT 11-plex were included to assess intra- and inter-batch variance at the protein and peptide level. This comprehensive human brain proteome and phosphoproteome dataset will serve as a valuable resource for the identification of biochemical, cellular and signaling pathways altered during AD progression. Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12901817
登录
查看更多内容
DOI：
10.1074/jbc.m114.589309
发表时间：
2015-01-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Falcon B;Cavallini A;Angers R;Glover S;Murray TK;Barnham L;Jackson S;O'Neill MJ;Isaacs AM;Hutton ML;Szekeres PG;Goedert M;Bose S
通讯作者：
Bose S
DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
16.2
作者：
Bai, Bing;Wang, Xusheng;Peng, Junmin
通讯作者：
Peng, Junmin
影响因子：
46.9
作者：
Blagoev, B;Ong, SE;Mann, M
通讯作者：
Mann, M
影响因子：
12.3
作者：
Dalgleish, Raymond;Flicek, Paul;Maglott, Donna R.
通讯作者：
Maglott, Donna R.