THE CEREBROSPINAL FLUID AND PLASMA PROTEOMICS OF IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS

Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible cause of dementia characterized by impaired gait and cognition and by urinary incontinence. However, limited understanding of its molecular pathophysiology and its subtypes contributes to varied treatment outcomes. To predict disease severity and progression, individual CSF biomarkers such as amyloid-beta and tau have been used. Recently, alterations in CSF and plasma proteome have been associated with cognitive impairment, but the proteomics of iNPH remain largely unexplored. To address this, we investigated how the CSF and plasma proteome is associated with iNPH, its severity and treatment response. The study cohort consists of 324 iNPH patients and 106 non-iNPH individuals treated in Kuopio. Paired plasma and lumbar CSF samples underwent SomaScan aptamer-based proteomics (>11,000 proteins quantified). Additionally, iNPH patients have brain biopsy pathology as well as cognitive and gait test results. To discover how iNPH is manifested in the human proteome, we ran linear model differential expression analyses using limma and SomaDataIO R packages on iNPH diagnosis status, severity and treatment response. The biological mechanisms underlying the associated proteins were interpreted with the help of pathway analysis and by finding tissues that each protein originates from. Preliminary results revealed 138 CSF and 975 plasma proteins significantly altered in iNPH vs non-iNPH group (adj.p < 0.05, |log2FC| > 1). We conclude that iNPH leaves a significant mark on both CSF and plasma proteome. Further analysis should advance our understanding of iNPH physiology and help identify novel disease mechanisms.