Objective: To investigate and identify biomarkers for PD from human olfactory cleft mucus

Background: Olfactory loss is an early symptom of PD, often preceding motor symptoms by years. However, hyposmia is not specific for PD, and the underlying triggers of olfactory loss at the molecular level are expected to vary among different causes. Based on this hypothesis, molecular biomarkers from olfactory tissue may be able to improve PD diagnosis at the earliest stages. Therefore, in this study we are collecting olfactory cleft mucus from PD patients and age-matched controls and using molecular biomarker assays to identify potential biomarkers for PD

Method: Subjects with a clinical diagnosis of PD and control subjects without parkinsonism or active sinonasal disease are recruited from the CMCVAMC PADRECC and ENT clinics. Olfactory mucus is collected by placing specialized sponges in the olfactory groove between the middle turbinate and superior nasal septum under direct endoscopic visualization. After 10 min in the nose, sponges are placed in microfuge tubes, centrifuged at 10,000 rpm for 2 min. Olfactory mucus is collected,  aliquoted, snap frozen on dry ice, and stored at -80°C for batch processing. Putative protein biomarkers will be measured using Luminex-based multiplex immunoassays

Results: We have recruited and collected olfactory mucus from 36 PD subjects and 12 controls (target 40 per group).  PD subjects are similar in age to controls (73.8±6.9 vs 68.3±10.3, p=0.11) but have worse olfactory performance (BSIT 5.0±2.4 vs 7.9±2.4, p=0.002).  Preliminary results from our prior proteomic analyses showed that the α-Syn to DJ-1 ratio in olfactory mucus is significantly increased in PD patients relative to age-matched controls (p=0.0009) and has a strong biomarker potential (AUC = 0.907). We will present results testing the α-Syn /DJ-1 ratio from samples in the full cohort as well as candidates derived from machine learning-based unbiased biomarker discovery approaches.

Conclusion: Non-invasive olfactory cleft mucus sampling potentially offers a rich source for targeted and unbiased discovery of PD biomarkers

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-disease-biomarkers-in-human-olfactory-cleft-mucus/