Proteomic Profiling of Nasal Fluid from the Brain-Nose Interface using Mass Spectrometry
Mueller, S. A.; Feng, X.; Babu, M.; Mertzig, S.; Metzler, R.; Wunderlich, H.; Weiss, G.; Bashiri, M.; Peters, O.; Froelich, L.; Wiltfang, J.; Oberstein, T. J.; San Nicolo, M.; Lichtenthaler, S. F.; Albert, M.
Show abstract
Nasal fluid collected at the brain-nose interface (BNI) may provide a minimally invasive window into central nervous system (CNS) biology, but its suitability for deep, reproducible proteomics remains unclear. Here, we establish and benchmark a standardized liquid chromatography-tandem mass spectrometry workflow for BNI proximal nasal fluid and compare its proteome to matched cerebrospinal fluid (CSF) from 40 individuals with cognitive impairment. Using pooled nasal fluid, we identified single pot, solid phase sample preparation combined with data independent acquisition (DIA) as the optimal strategy, with low coefficients of variation. In cognitively impaired cohort, DIA based proteomics on a timsTOF pro quantified on average 5,210 proteins in nasal fluid and 1,800 in CSF, with 4,901 nasal fluid proteins detected in at least 75% of samples. Nasal fluid contained nearly 50% of the CSF proteome (876 shared proteins), including numerous CNS and neurodegeneration associated species. The result of this exploratory study position BNI derived nasal fluid as a robust, proteome rich biofluid for proteomics driven CNS biomarker research.
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