Kamalian et al. conducted an in-depth [[proteomics]] of [[cerebrospinal fluid]] (CSF) in 28 shunt-responsive [[idiopathic normal pressure hydrocephalus]] patients, 38 Mild [[Cognitive Impairment]] (MCI) due to [[Alzheimer's disease]], and 49 healthy controls. Utilizing the Olink Explore 3072 panel, they 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 [[ependyma]]l 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 [[idiopathic normal pressure hydrocephalus pathophysiology]], with implications for improved [[idiopathic normal pressure hydrocephalus diagnosis]] ((Kamalian A, Shirzadeh Barough S, Ho SG, Albert M, Luciano MG, Yasar S, Moghekar A. Molecular [[signature]]s of normal pressure hydrocephalus: a large-scale proteomic analysis of cerebrospinal fluid. Fluids Barriers CNS. 2024 Aug 8;21(1):64. doi: 10.1186/s12987-024-00561-5. PMID: 39118132.)).