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

Product:

CNS Disease Panel 120

Topic:

CNS

Disease Area:

Alzheimer's Disease

Sample Type:

CSF, Nasal Fluid, Plasma

Topic/Product:

CNS Disease Panel 120

Disease Area:

Alzheimer's Disease

Sample Type:

CSF, Nasal Fluid, Plasma

Abstract

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, α-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.

Authors & Affiliations

Mohammad Bashiriᵃ, Maria Babuᵃ, Gunter Weissᵃ, Stefan Kotschoteᵃ, Richard Metzlerᵃ, Hilary Wunderlichᵃ, Agnese Petreraᵇ, Elena De Domenicoᶜ, Heidi Theisᶜ, Katrin Lehmannᵈ, Frederik Heinrichᵈ, Mir-Farzin Mashreghiᵈ, Marion San Nicolóᵃ, Mareike Albertᵃ, and Sabine Mertzigᵃ*

ᵃ Noselab GmbH, Widenmayerstrasse 27, 80538, Munich, Germany
ᵇ Metabolomics and Proteomics Core, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany
ᶜ PRECISE Platform for Genomics and Epigenomics at German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
ᵈ Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin

* Corresponding author: Sabine Mertzig

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition. He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.