Kamalian Aida, Barough Siavash Shirzadeh, Ho Sara G, Albert Marilyn, Luciano Mark G, Yasar Sevil, Moghekar Abhay
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
bioRxiv. 2024 Mar 4:2024.03.01.583014. doi: 10.1101/2024.03.01.583014.
Given the persistent challenge of differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from similar clinical entities, we conducted an in-depth proteomic study of cerebrospinal fluid (CSF) in 28 shunt-responsive iNPH patients, 38 Mild Cognitive Impairment (MCI) due to Alzheimer's disease, and 49 healthy controls. Utilizing the Olink Explore 3072 panel, we identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside vimentin and inflammatory markers upregulation, these results suggest ependymal layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with congenital hydrocephalus (e.g., L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1) points to a possible shared molecular foundation between congenital hydrocephalus and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the pathophysiology of iNPH, with implications for improved diagnosis.
鉴于鉴别特发性正常压力脑积水（iNPH）与类似临床病症一直存在挑战，我们对28例分流反应性iNPH患者、38例因阿尔茨海默病导致的轻度认知障碍（MCI）患者以及49名健康对照者的脑脊液（CSF）进行了深入的蛋白质组学研究。利用Olink Explore 3072检测板，我们在iNPH中鉴定出了独特的蛋白质组学特征，突出显示了突触标记物和细胞间粘附蛋白的显著下调。除波形蛋白和炎症标记物上调外，这些结果提示室管膜层和经室管膜流动功能障碍。此外，与先天性脑积水相关的多种蛋白质（如L1CAM、PCDH9、ISLR2、ADAMTSL2和B4GAT1）的下调表明先天性脑积水和iNPH之间可能存在共同的分子基础。通过正交偏最小二乘判别分析（OPLS-DA），已确定一个由13种蛋白质组成的检测板作为iNPH的潜在诊断生物标志物，有待外部验证。这些发现为iNPH的病理生理学提供了新的见解，对改善诊断具有重要意义。
