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Abstract Details

Deep Proteomics Profiling of Cerebrospinal Fluid in Idiopathic Normal Pressure Hydrocephalus and Mild Cognitive Impairment
General Neurology
P11 - Poster Session 11 (5:30 PM-6:30 PM)
4-006
iNPH is manifested with a triad of cognitive impairment, urinary incontinence, and gait abnormalities. The CSF proteomics of iNPH and its etiology remain unknown.  
To discover novel cerebrospinal fluid (CSF) biomarkers relevant to Idiopathic Normal Pressure Hydrocephalus (iNPH)
CSF samples were collected from 50 HC (68.6 ± 6.2 years), 29 iNPH patients (71.5 ± 5.1 years) that were found to benefit significantly from shunt surgery in subsequent follow-ups, and 38 Mild Cognitive Impairment (MCI) participants (75.0 ± 9.2 years) with positive CSF Alzheimer’s disease (AD) biomarkers. We used Olink Explore 3072 platform to map approximately 3000 proteins in the CSF samples and then performed Welch’s t-test, analysis of variance (ANOVA), and Kruskal-Wallis (KW) analyses for statistical analysis using R v4.3.1. Then, we performed over-representation analysis (ORA) and gene set enrichment analysis (GSEA) using R.
583 proteins were differentially expressed in iNPH compared to HC (416 down- and 167 upregulated). 1675 proteins were found to be differentially expressed based on ANOVA and KW testing between iNPH, MCI, and HC. The pathway analysis of the data demonstrated significant downregulation of pathways related to “Neuronal cell-cell adhesion” (NRXN3, CNTNAP2, DSCAM), “synaptic signaling” (GRIK2, RTN4R, NPTX1, NPTX2, NPTXR, TMEM25, SNAP25, SNAPIN, NRGN), and a known congenital hydrocephalus marker, L1CAM. In contrast, “lymphocytic chemotaxis” and “chemokine-related” pathways were found to be significantly upregulated in iNPH (CCL2, CXCL10, CXCL9, GBP2). Additionally, known AD protein markers such as MAPT, TREM2, GFAP, SCRN1 were not differentially expressed in iNPH. NEFL was significantly upregulated in both MCI and iNPH. Proteins constitutively secreted by choroid plexus (ENPP2, TTR) were not differentially expressed in iNPH.

While synaptic and neuronal adhesion pathways are downregulated in iNPH, lymphocytic chemotaxis and neuroinflammatory markers are upregulated and these changes are not accounted for by the increased CSF volume of distribution.

Authors/Disclosures
Aida Kamalian, MD, MPH (Johns Hopkins Univeresity)
PRESENTER
Dr. Kamalian has nothing to disclose.
Megha Patel (Johns Hopkins University) No disclosure on file
Sara Ho No disclosure on file
Abhay Moghekar, MD (Johns Hopkins Bayview Medical Center) Dr. Moghekar has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Deluca and Weizenbaum. Dr. Moghekar has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Silver Golub and Tieteel. Dr. Moghekar has a non-compensated relationship as a Medical Advisory Board member with Hydrocephalus Association that is relevant to AAN interests or activities. Dr. Moghekar has a non-compensated relationship as a Medical Advisory Board member with Spinal CSF Leak Foundation that is relevant to AAN interests or activities.