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

Abstract

Olfactory dysfunction manifests in early stages of neurodegeneration in several disorders of the central nervous system. The sense of smell is orchestrated by the cells of the olfactory mucosa located in the upper nasal cavity, however, it is unclear how this tissue reflects key neurodegenerative features in Alzheimer’s disease (AD). Here we report that olfactory mucosa (OM) cells of patients with AD secrete increased amounts of toxic amyloid-beta. We detail cell-type specific gene expression patterns, unveiling 154 differentially expressed AD-associated genes compared to the cognitively normal controls, and 5 distinct cell populations in the cultures, together with disease-associated subpopulations. Overall, coordinated alteration of RNA and protein metabolism, inflammatory processes and signal transduction were observed in multiple cell types, suggesting a key role in AD pathophysiology. Our results demonstrate the potential of OM cultures as a new cellular model for AD. Moreover, for the first time we provide single cell transcript data for investigating the molecular and cellular mechanisms of AD in the OM.