6th Edition of Neurology World Conference 2026

Abstract

Background: Hearing loss in patients with vestibular schwannoma (VS), whether sporadic or associated with NF2-related schwannomatosis (NF2-SWN), cannot be fully explained by tumor size or location alone. A literature review of 32 studies investigating schwannomas, perilymph, and hearing loss revealed that elevated proteins, including VEGF, ADAM9, and MMPs, are frequently detected in perilymph. While most studies used human tissue (n=31), murine models have shown promise for mechanistic validation. We hypothesize that across human and mouse models of NF2-SWN, protein precipitates contribute to hearing loss through mechanisms involving cell cytotoxicity or altered peri- and endolymphatic pressure within the cochlear and vestibular compartments. Methods: This study integrates mass spectrometry protein profiling of cochlear fluids from genetically engineered NF2-SWM mouse models, P0-NF2∆2-3 and Postn-Cre; Nf2flox/flox, followed by immunohistochemical staining (IHC) of the mouse inner ear, ganglia, and tumor tissues to validate candidate biomarkers. In addition, IHC will be conducted on human temporal bone samples from VS patients to evaluate cross-species expression of identified proteins. Results: Protein precipitates were identified in the two P0-NF2∆2-3 and Postn-Cre; Nf2flox/flox mouse models, recapitulating human findings. Mass spectrometry has revealed distinct expression profiles in normal and mutant mouse cochlear fluids, and validation by IHC in mouse and human samples is underway. Conclusions: The presence of protein precipitates in both human and mouse models presenting with hearing loss supports the contribution of protein precipitates to the mechanism of hearing loss in NF2-SWN patients. We show the feasibility of mass spectrometry in micro amounts of cochlear fluids from mice, opening the way to studies on the cellular origin of these proteins.