Disease specific alterations in the olfactory mucosa of patients with Alzheimer's disease

Abstract

Olfactory dysfunction manifests early in several neurodegenerative disorders. Olfaction is orchestrated by olfactory mucosal cells located in the upper nasal cavity. However, it is unclear how this tissue reflects key neurodegenerative features in Alzheimers disease. Here we report that Alzheimers disease olfactory mucosal cells obtained from live individuals secrete toxic amyloid-beta. We detail cell-type-specific gene expression patterns, unveiling 147 differentially expressed disease-associated genes compared to the cognitively healthy controls, and 5 distinct populations in globose basal cell -, myofibroblast-, and fibroblast/ stromal - like cells in vitro. Overall, coordinated alteration of RNA and protein metabolism, inflammatory processes and signal transduction were observed in multiple cell populations, suggesting a key role in pathophysiology. Our results demonstrate the potential of olfactory cell cultures in modelling Alzheimers disease advocate their use for diagnostic purposes. Moreover, for the first time we provide single cell data on olfactory mucosa in Alzheimers disease for investigating molecular and cellular mechanisms associated with the disease.