Insights Into Nasal Pathways for Brain Protein Sampling and Treatment Delivery: Mony de Leon, EdD

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We observed that the flow from the brain was reduced in patients with amyloid. In the nose, we saw the same thing, that the outflow was reduced."

Previous studies suggest that a reduction of clearance in cerebrospinal fluid (CSF) may be a pathological feature of Alzheimer disease (AD). Findings from nonhuman mammals and contradictory human neuroimaging data showed that it has remained questionable whether the nasal mucosa is a CSF drainage site among patients. A newly published study in Fluids and Barriers of the CNS used dynamic PET with [1-11C]-Butanol, a highly permeable radiotracer with no appreciable brain binding, to examine whether brain and nasal fluid drainage times were correlated and affected by brain amyloid.¹

Led by Mony de Leon, EdD, 24 cognitively normal participants at least 65 years of age were dynamically PET imaged for 60 minutes using [1-11C]-Butanol. Imaging with either [11C]-PiB or [18F]-FBB recognized 8 amyloid PET positive (Aβ+) and 16 Aβ- participants. MRI-determined regions of interest included carotid artery, lateral orbitofrontal brain, cribriform plate, and an all-turbinate region comprised of the superior, middle, and inferior turbinates. Additional findings showed that the lateral orbitofrontal brain All-turbinate regions showed a positive association, which suggested a connection between the brain and the nose.

de Leon, director of the Brain Health Imaging Institute and professor of neuroscience in the department of radiology at Weill Cornell Medicine, recently sat down with NeurologyLive^® in an interview to discuss how nasal pathways can be utilized for noninvasive brain protein sampling. He also talked about the implications of using nasal pathways for drug delivery to the brain, as gathered from the implications of the study. Additionally, de Leon spoke about how the nasal-brain interface may impact the regulation of brain protein outflow and immune system interactions.

REFERENCES
1. Mehta NH, Wang X, Keil SA, et al. [1-11C]-Butanol Positron Emission Tomography reveals an impaired brain to nasal turbinates pathway in aging amyloid positive subjects. Fluids Barriers CNS. 2024;21(1):30. Published 2024 Apr 2. doi:10.1186/s12987-024-00530-y