Molecular analysis of nasal secretion to identify Alzheimer’s disease

Abstract

AbstractBackgroundIncreasing clinical evidence shows significant drainage of cerebrospinal fluid (CSF) and its metabolites along the olfactory route into the nose. Nasal secretion‐based analysis of key Alzheimer biomarkers was compared to CSF‐based analysis in different cohorts.MethodWe conducted a multicenter, prospective cohort study involving patients with cognitive impairment and availability of CSF measurement of the 4 AD‐specific proteins. Cohorts were defined based on CSF biomarker classification following NIA‐AA ATN research diagnostic framework and clinical findings. Nasal secretion (NS) was collected from the vicinity of the olfactory cleft. [NosetestAD] was performed for subsequent in vitro analysis.ResultFor this analysis, 39 patients with cognitive impairment were included at 3 university clinics in Germany. The nasal sampling procedure [noseabsorb] is painless (VAS 2 ±1.7) and yields a high sample volume (mean 450 μl). [NosetestAD] allows for precise quantification in size and relative protein amount of AD biomarkers pTau181, total Tau, Amyloid‐ß1‐40 and Amyloid‐ß1‐42. By using an automated protein separation and immunodetection system, we are able to generate a protein specific biomarker signature for all 4 AD‐associated proteins (pTau, tTau, Aß42,Aß40) characterizing parameters such as oligomerization state and relative protein amount. Further, a highly significant discrimination of amyloid pathology (A+ vs. A‐) was achieved with an AUC of 0.94 and p‐value <0.001.ConclusionNasal secretion constitutes a safe, minimally invasive access to CSF. Therefore, it is highly suitable for detection and monitoring of AD relevant biomarkers. Within a cohort of patients with cognitive impairment A+ patients can be distinguished from A‐ patients based on their diseases state specific individual protein‐specific biomarker signatures and the different levels of oligomeric or monomeric structures. Thus, our proprietary diagnostic platform, detects and assesses a broad panel of brain derived biomarkers simultaneously and allows for intraindividual monitoring and possibly disease staging in nasal secretion.