Nanoparticle-Enabled Enrichment of Longitudinal Blood Proteomic Fingerprints in Alzheimer's Disease.
Nanoparticle-Enabled Enrichment of Longitudinal Blood Proteomic Fingerprints in Alzheimer's Disease.
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纳米颗粒使阿尔茨海默病患者纵向血液蛋白质组指纹图谱的浓缩。
DOI：
10.1021/acsnano.1c00658
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发表时间：
2021-04-27
期刊：
影响因子：
17.1
通讯作者：
Kostarelos K
中科院分区：
文献类型：
--
作者：
Hadjidemetriou M;Rivers-Auty J;Papafilippou L;Eales J;Kellett KAB;Hooper NM;Lawrence CB;Kostarelos K
血液循环生物标志物有可能在临床症状出现之前检测阿尔茨海默病（AD）的病理，并改善疾病改善疗法的临床试验结果。尽管最近在了解伴随的全身异常方面取得了进展，但目前还没有经过验证或临床使用的基于血液的AD生物标志物。血液中神经变性相关蛋白的浓度极低，需要开发分析平台来解决“信噪比”问题，并允许对血浆蛋白质组进行深入分析。在这里，我们的目的是发现和纵向跟踪阿尔茨海默病转基因小鼠模型的血液蛋白质组的变化，使用纳米颗粒为基础的蛋白质组富集方法。我们利用血液循环、基于脂质的纳米颗粒来提取、分析和监测AD特异性蛋白质特征，并系统地揭示与AD进展相关的分子途径。我们的数据显示血液中存在多种蛋白质组学信号，表明AD的无症状阶段。通过无标记液相色谱-串联质谱法对纳米颗粒回收的血液蛋白质组进行综合分析，发现了ad监测特征，可以将无症状期与淀粉样变性和认知衰退区分开来。虽然大多数差异丰富的血浆蛋白在初始无症状阶段被发现上调，但这些分子的丰度由于淀粉样变而显着降低，这表明ad特异性血液蛋白质组的波动与疾病阶段相关。所提出的纳米组学方法的潜在用途是揭示血液中与脑神经变性直接相关的信息，这进一步证明了局灶黏附级联蛋白的恢复。在此，我们建议将纳米技术与现有的蛋白质组学分析工具相结合，以丰富对神经退行性疾病血液循环信号的识别，重新激活血液蛋白质组学在预测阿尔茨海默病发病和进展轨迹方面的潜在临床应用。
Blood-circulating biomarkers have the potential to detect Alzheimer’s disease (AD) pathology before clinical symptoms emerge and to improve the outcomes of clinical trials for disease-modifying therapies. Despite recent advances in understanding concomitant systemic abnormalities, there are currently no validated or clinically used blood-based biomarkers for AD. The extremely low concentration of neurodegeneration-associated proteins in blood necessitates the development of analytical platforms to address the “signal-to-noise” issue and to allow an in-depth analysis of the plasma proteome. Here, we aimed to discover and longitudinally track alterations of the blood proteome in a transgenic mouse model of AD, using a nanoparticle-based proteomics enrichment approach. We employed blood-circulating, lipid-based nanoparticles to extract, analyze and monitor AD-specific protein signatures and to systemically uncover molecular pathways associated with AD progression. Our data revealed the existence of multiple proteomic signals in blood, indicative of the asymptomatic stages of AD. Comprehensive analysis of the nanoparticle-recovered blood proteome by label-free liquid chromatography–tandem mass spectrometry resulted in the discovery of AD-monitoring signatures that could discriminate the asymptomatic phase from amyloidopathy and cognitive deterioration. While the majority of differentially abundant plasma proteins were found to be upregulated at the initial asymptomatic stages, the abundance of these molecules was significantly reduced as a result of amyloidosis, suggesting a disease-stage-dependent fluctuation of the AD-specific blood proteome. The potential use of the proposed nano-omics approach to uncover information in the blood that is directly associated with brain neurodegeneration was further exemplified by the recovery of focal adhesion cascade proteins. We herein propose the integration of nanotechnology with already existing proteomic analytical tools in order to enrich the identification of blood-circulating signals of neurodegeneration, reinvigorating the potential clinical utility of the blood proteome at predicting the onset and kinetics of the AD progression trajectory.
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影响因子：
6.8
作者：
Chatterjee P;Pedrini S;Stoops E;Goozee K;Villemagne VL;Asih PR;Verberk IMW;Dave P;Taddei K;Sohrabi HR;Zetterberg H;Blennow K;Teunissen CE;Vanderstichele HM;Martins RN
通讯作者：
Martins RN
影响因子：
9.3
作者：
Fonseca, Maria I.;Chu, Shu-Hui;Tenner, Andrea J.
通讯作者：
Tenner, Andrea J.
影响因子：
4.8
作者：
Lopez, Oscar L.;Klunk, William E.;Kuller, Lewis H.
通讯作者：
Kuller, Lewis H.
影响因子：
14
作者：
Hadjidemetriou, Marilena;Al-ahmady, Zahraa;Kostarelos, Kostas
通讯作者：
Kostarelos, Kostas
影响因子：
16.6
作者：
Blume, John E.;Manning, William C.;Farokhzad, Omid C.
通讯作者：
Farokhzad, Omid C.