瑞典隆德大学Oskar Hansson等研究人员合作揭示，与渐进性Aβ斑块和tau缠结病理相关的阿尔茨海默病蛋白质组学变化。相关论文于2024年8月26日在线发表在《自然—神经科学》杂志上。

结合放射性配体测量β-淀粉样蛋白（Aβ）斑块和tau缠结与脑脊液蛋白质组学分析，研究人员发现了反映阿尔茨海默病（AD）病理不同阶段的分子事件。在整个AD谱系中，研究人员发现了127种差异丰富的蛋白质（DAP）。

最强的Aβ相关蛋白主要在胶质细胞中表达，包括SMOC1和ITGAM。与tau缠结负荷和tau积累独立相关的有十几种与ATP代谢相关并优先在神经元中表达的蛋白质。

仅有20%的DAP在其他神经退行性疾病中也发生变化，突显出AD独特的蛋白质组特征。与蛋白质代谢和小胶质细胞免疫反应相关的两个共表达模块包含了大多数DAP，并沿着AD连续体表现出相反的、错位的轨迹。

研究人员揭示了与Aβ和tau蛋白病相关的体内蛋白质特征，为复杂的神经反应以及针对不同疾病阶段的潜在生物标志物和治疗手段提供了新的见解。

据介绍，蛋白质组学能够揭示像AD这样复杂的神经退行性疾病中的动态和多方面的变化。

附：英文原文

Title: Proteomic changes in Alzheimer disease associated with progressive Aβ plaque and tau tangle pathologies

Author: Pichet Binette, Alexa, Gaiteri, Chris, Wennstrm, Malin, Kumar, Atul, Hristovska, Ines, Spotorno, Nicola, Salvad, Gemma, Strandberg, Olof, Mathys, Hansruedi, Tsai, Li-Huei, Palmqvist, Sebastian, Mattsson-Carlgren, Niklas, Janelidze, Shorena, Stomrud, Erik, Vogel, Jacob W., Hansson, Oskar

Issue&Volume: 2024-08-26

Abstract: Proteomics can shed light on the dynamic and multifaceted alterations in neurodegenerative disorders like Alzheimer disease (AD). Combining radioligands measuring β-amyloid (Aβ) plaques and tau tangles with cerebrospinal fluid proteomics, we uncover molecular events mirroring different stages of AD pathology in living humans. We found 127 differentially abundant proteins (DAPs) across the AD spectrum. The strongest Aβ-related proteins were mainly expressed in glial cells and included SMOC1 and ITGAM. A dozen proteins linked to ATP metabolism and preferentially expressed in neurons were independently associated with tau tangle load and tau accumulation. Only 20% of the DAPs were also altered in other neurodegenerative diseases, underscoring AD’s distinct proteome. Two co-expression modules related, respectively, to protein metabolism and microglial immune response encompassed most DAPs, with opposing, staggered trajectories along the AD continuum. We unveil protein signatures associated with Aβ and tau proteinopathy in vivo, offering insights into complex neural responses and potential biomarkers and therapeutics targeting different disease stages.

DOI: 10.1038/s41593-024-01737-w

Source: https://www.nature.com/articles/s41593-024-01737-w