Distinguishing Alzheimer's Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis.
Distinguishing Alzheimer's Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis.
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DOI：
10.3390/brainsci11050583
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发表时间：
2021-04-30
期刊：
影响因子：
3.3
通讯作者：
Hershey LA
中科院分区：
文献类型：
--
作者：
Hanas JS;Hocker JRS;Vannarath CA;Lerner MR;Blair SG;Lightfoot SA;Hanas RJ;Couch JR;Hershey LA
重要的是开发微创生物标志物平台，以帮助识别和监测阿尔茨海默病（AD）患者。帮助理解生物化学机制以及识别潜在的新型生物标志物和治疗靶点将是此类平台的额外好处。这项研究利用了一个简化的和新的血清分析平台，使用质谱（MS），以帮助区分AD患者组（轻度和中度）和对照组，以及帮助了解生化表型和可能的疾病发展。采用留一[血清样本]交叉验证（LOOCV）结合新的峰分类评价（PCV）程序，对AD患者和对照个体之间的血清质量峰进行比较。LOOCV/PCV能够区分一组轻度AD患者和对照个体之间的显著血清质量峰值差异，p值为10−13。当在两组之间随机分配相同的血清样本并通过LOOCV/PCV重新分析时，该值变得不显著（p = 0.09）。这表明原始真实病理学二元组比较中的生理组差异。AD患者和创伤性脑损伤（TBI）患者之间的相似性和差异也可使用这种新型LOOCV/PCV平台辨别。对血清质量峰进行MS/MS肽分析，将轻度AD患者与对照个体进行比较。生物信息学分析表明，AD中受影响的细胞途径/生化表型包括涉及神经元细胞死亡、血管系统、神经发生和AD/痴呆/淀粉样变性的细胞途径/生化表型。炎症、自身免疫、自噬和血脑屏障途径似乎也与AD相关。与F8（因子VIII）和LRP 1和NOTCH 1连接的VWF/ADAMTS 13血管轴受损，并被认为在AD发展中很重要。
It is important to develop minimally invasive biomarker platforms to help in the identification and monitoring of patients with Alzheimer’s disease (AD). Assisting in the understanding of biochemical mechanisms as well as identifying potential novel biomarkers and therapeutic targets would be an added benefit of such platforms. This study utilizes a simplified and novel serum profiling platform, using mass spectrometry (MS), to help distinguish AD patient groups (mild and moderate) and controls, as well as to aid in understanding of biochemical phenotypes and possible disease development. A comparison of discriminating sera mass peaks between AD patients and control individuals was performed using leave one [serum sample] out cross validation (LOOCV) combined with a novel peak classification valuation (PCV) procedure. LOOCV/PCV was able to distinguish significant sera mass peak differences between a group of mild AD patients and control individuals with a p value of 10−13. This value became non-significant (p = 0.09) when the same sera samples were randomly allocated between the two groups and reanalyzed by LOOCV/PCV. This is indicative of physiological group differences in the original true-pathology binary group comparison. Similarities and differences between AD patients and traumatic brain injury (TBI) patients were also discernable using this novel LOOCV/PCV platform. MS/MS peptide analysis was performed on serum mass peaks comparing mild AD patients with control individuals. Bioinformatics analysis suggested that cell pathways/biochemical phenotypes affected in AD include those involving neuronal cell death, vasculature, neurogenesis, and AD/dementia/amyloidosis. Inflammation, autoimmunity, autophagy, and blood–brain barrier pathways also appear to be relevant to AD. An impaired VWF/ADAMTS13 vasculature axis with connections to F8 (factor VIII) and LRP1 and NOTCH1 was indicated and is proposed to be important in AD development.
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影响因子：
9.9
作者：
Ewers, M.;Buerger, K.;Hampel, H.
通讯作者：
Hampel, H.
DOI：
10.1038/s41582-018-0079-7
发表时间：
2018-11
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
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通讯作者：
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影响因子：
4
作者：
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通讯作者：
Srivastava, Sudhir
影响因子：
2.8
作者：
Crehan, Helen;Holton, Patrick;Hardy, John
通讯作者：
Hardy, John
影响因子：
3
作者：
Guan W;Zhou M;Hampton CY;Benigno BB;Walker LD;Gray A;McDonald JF;Fernández FM
通讯作者：
Fernández FM