Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Biomolecules. 2023 Jul 8;13(7):1094. doi: 10.3390/biom13071094.
(1) Background: Despite the existence of well-established, CSF-based biomarkers such as amyloid-β and phosphorylated-tau, the pathways involved in the pathophysiology of Alzheimer's disease (AD) remain an active area of research. (2) Methods: We measured 3072 proteins in CSF samples of AD-biomarker positive mild cognitive impairment (MCI) participants ( = 38) and controls ( = 48), using the Explore panel of the Olink proximity extension assay (PEA). We performed group comparisons, association studies with diagnosis, age, and APOE ε4 status, overrepresentation analysis (ORA), and gene set enrichment analysis (GSEA) to determine differentially expressed proteins and dysregulated pathways. (3) Results: GSEA results demonstrated an enrichment of granulocyte-related and chemotactic pathways (core enrichment proteins: ITGB2, ITGAM, ICAM1, SELL, SELP, C5, IL1A). Moreover, some of the well-replicated, differentially expressed proteins in CSF included: ITGAM, ITGB2, C1QA, TREM2, GFAP, NEFL, MMP-10, and a novel tau-related marker, SCRN1. (4) Conclusion: Our results highlight the upregulation of neuroinflammatory pathways, especially chemotactic and granulocyte recruitment in CSF of early AD patients.
(1) 背景：尽管存在成熟的基于 CSF 的生物标志物，如淀粉样蛋白-β和磷酸化 tau，但阿尔茨海默病（AD）的病理生理学涉及的途径仍然是一个活跃的研究领域。(2) 方法：我们使用 Olink proximity extension assay（PEA）的 Explore 面板，测量了 AD 生物标志物阳性轻度认知障碍（MCI）参与者（=38）和对照组（=48）的 CSF 样本中的 3072 种蛋白质。我们进行了组间比较、与诊断、年龄和 APOE ε4 状态的关联研究、过度表达分析（ORA）和基因集富集分析（GSEA），以确定差异表达的蛋白质和失调的途径。(3) 结果：GSEA 结果表明，粒细胞相关和趋化途径富集（核心富集蛋白：ITGB2、ITGAM、ICAM1、SELL、SELP、C5、IL1A）。此外，CSF 中一些复制良好的差异表达蛋白包括：ITGAM、ITGB2、C1QA、TREM2、GFAP、NEFL、MMP-10 和一种新的 tau 相关标志物 SCRN1。(4) 结论：我们的结果强调了神经炎症途径的上调，尤其是趋化和粒细胞在早期 AD 患者 CSF 中的募集。
