Targeted Proteomic Profiling of Nasal Fluid from the Brain-Nose Interface

The brain-nose interface is an anatomical junction where olfactory neurons from the olfactory bulb traverse the cribriform plate into the nasal mucosa, providing minimally invasive access to the central nervous system (CNS). We hypothesized that nasal fluid from this region could enable detection of neurology-relevant proteins using targeted multiplex assays. Using nosecollect, a targeted nasal sampling device, nasal fluid proximal to brain-nose interface was collected from cognitively impaired patients, alongside matched cerebrospinal fluid (CSF) and plasma. After nasal sample-specific dilution optimization and intra-assay precision evaluation, all matrices were profiled with the Olink Target 96 Neurology and NUcleic acid Linked Immuno-Sandwich Assay CNS disease 120 (NULISAseq CNS Disease 120) panels. Nasal fluid showed technically repeatable detection (intra-assay coefficient of variation <10% for more than 60% of proteins). Target detectability in nasal fluid (Olink 89/92; NULISA 121/131 proteins) was comparable to plasma and exceeded CSF. Numerous disease-relevant proteins were observed in nasal fluid, including brain-derived tau species, phosphorylated tau, alpha-synuclein, axonal and synaptic markers, and glial-microglial mediators. To our knowledge, this is the first neurology-focused characterization of the nasal proteome from the vicinity of brain-nose interface using targeted multiplex platforms and the first to profile matched nasal fluid, CSF, and plasma, supporting nasal fluid from brain-nose interface as an additional source for biomarker development.