Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8654, Japan.
Life Sciences Core Facility, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Sci Rep. 2024 Aug 27;14(1):19901. doi: 10.1038/s41598-024-71097-9.
Proximity Extension Assay (PEA) and mass spectrometry (MS) methodologies were utilized for the proteomic and lipidomic characterization of plasma specimens from patients who developed Alzheimer's disease. Proteomics was performed by both PEA and Liquid Chromatography (LC)/MS in this study, but all the more because LC/MS generally tends to be biased towards proteins with high expression and high variability, generating hypotheses proved challenging. Consequently, attempt was made to interpret the results from the PEA data. There were 150 significantly variable proteins and 68 lipids among 1000 proteins and 400 lipids. Pathway analysis was performed for both total and variable proteins measured to reduce bias, and it appeared that vascular fragility was related to AD. Furthermore, a multitude of lipid-associated proteins exhibited statistical changes. In certain instances, the function of individual proteins affected the factors associated with them, whereas others demonstrated trends contrary to anticipated outcomes. These trends seem indicative of diverse feedback mechanisms that provide homeostatic equilibrium. The degree of unsaturation of fatty acids, correlated with cardiovascular risk, warrants specific attention. Certain bile acids exhibited the potential to cause vascular endothelial damage. Contemplating these discoveries in tandem with previously documented phenomena, subtle shifts in homeostatic functions seem to be linked to the fragility of vascular endothelial cells. This is evidenced by the slow and chronic evolution of Alzheimer's disease from preclinical stages to its manifestation.
采用邻近延伸分析（PEA）和质谱（MS）方法对发生阿尔茨海默病的患者的血浆标本进行蛋白质组学和脂质组学分析。本研究中同时使用 PEA 和液相色谱（LC）/MS 进行蛋白质组学分析，但由于 LC/MS 通常偏向于高表达和高变异性的蛋白质，因此生成假设具有挑战性。因此，尝试从 PEA 数据中解释结果。在 1000 种蛋白质和 400 种脂质中，有 150 种蛋白质和 68 种脂质存在显著差异。对总蛋白和可变蛋白进行了通路分析，以减少偏倚，结果表明血管脆弱与 AD 相关。此外，许多与脂质相关的蛋白质也表现出统计学变化。在某些情况下，单个蛋白质的功能会影响与其相关的因素，而其他蛋白质则表现出与预期结果相反的趋势。这些趋势似乎表明存在多种反馈机制，以提供体内平衡。与心血管风险相关的脂肪酸不饱和程度值得特别关注。某些胆酸可能会导致血管内皮损伤。考虑到这些发现与之前记录的现象相结合，体内平衡功能的细微变化似乎与血管内皮细胞的脆弱性有关。这可以从阿尔茨海默病从临床前阶段到表现出的缓慢和慢性演变中得到证明。
