Antemortem biomarkers in nasally exhaled breath: A potential novel, noninvasive human diagnostic technique for Alzheimer’s Disease

Northwestern University At Chicago, Evanston IL

Investigators

Abstract

ABSTRACT The goal of this proposal is to test the hypothesis that nasally exhaled breath contains biomarkers of Alzheimer’s disease (AD). Preliminary data from our lab indicate that: (1) the neural protein Tau is present in nasally exhaled breath at higher concentrations than in orally exhaled breath, and (2) Tau concentration increases linearly with dementia severity in patients with AD. An established body of research indicates that exhaled breath contains a rich variety of biological molecules including proteins, cytokines, RNA, DNA and other biomarkers that originate along the lining of the respiratory tract. With the goal of measuring respiratory biomarkers, the vast majority of exhaled breath studies use orally exhaled breath; by contrast, very little research has focused on nasally exhaled samples. In this proposal, we aim to focus our research on nasally exhaled breath in order to test the hypothesis that the unique anatomy of this exhalation route provides direct access to neural biomarkers of AD. Specifically, human olfactory sensory neurons constitute the only part of the central nervous system that makes direct contact with the external environment. The cilia on their peripheral ends protrude from the olfactory mucosa into the nasal cavity, while the central ends project through holes in the cribriform plate at the base of the skull and synapse directly onto the brain. The human cribriform plate is also a drainage pathway for cerebrospinal fluid. As a result of these unique anatomical circumstances, chemical constituents of the central nervous system are present in the olfactory mucosa inside the nose, likely due to nasally exhaled air flowing turbulently over the olfactory mucosa and volatilizing proteins in this region. In this proposal, we aim to explore the novel idea that these volatilized neural proteins can be collected in nasally exhaled breath and quantitated. To test this notion, we will first examine the hypothesis that biomarkers of neurological disease (Tau, beta-amyloid) can be quantitated noninvasively by collecting nasally and orally exhaled breath from patients currently diagnosed with AD, and comparing levels of biomarker concentration across nasal and oral samples. Second, we will compare levels of biomarkers concentration (nasal, oral) across three groups of participants: patients with AD, age-matched healthy controls, and healthy young adults. Across the proposed experiments, we will also look for correlations between nasally (vs. orally) exhaled proteins and disease severity. If successful, results from the proposed studies could aid in the development of a novel, noninvasive and inexpensive diagnostic tool for ADRD and other neurological diseases that could offer mobility and accessibility for at-home testing. Future research in this direction would not only be clinically valuable but could also leave a broader scientific impact by initiating a step forward in advancing current limits of real-time human brain chemistry measurement.