Olfactory Mucosal Cells of Individuals with Alzheimer’s Disease Display Alterations Similar to the Alzheimer Brain

Abstract

AbstractBackgroundA sense of smell is orchestrated in the first place by the cells of the olfactory mucosa (OM), located in the rooftop of the nasal cavity. Impairments in olfaction are implicated in aging but also in Alzheimer’s disease (AD). Here, we describe the observed alterations in cultures of OM cells derived from individuals with late‐onset AD or amnestic form of mild cognitive impairment (MCI) when compared to OM cells derived from their cognitively healthy control subjects.MethodPrimary cultures of OM cells were harvested from biopsies of OM derived from cognitively healthy individuals and individuals with late‐onset AD or amnestic MCI and cultured in vitro. First, the cell types present in cultures of OM cells and genes differentially expressed between the OM cells derived from control subjects and individuals AD or MCI OM were assessed by single cell RNA‐sequencing (scRNA‐seq). Next, a total RNA‐seq was applied to a larger cohort of samples. The results of total and scRNA‐seq were further validated with various functional in vitro assays including inductively coupled plasma mass spectrometry (ICP‐MS) and measurements of intracellular ATP levels.ResultThe scRNA‐seq unveiled a total of five distinct cell populations in OM cell cultures. A total of 240 previously AD‐related genes were found to be differentially expressed between the AD and control OM cell cultures. Similarly, the MCI OM cells harbored 224 differentially expressed genes when compared to OM cells derived from their control subjects. Common for both AD and MCI OM cells were the alterations in genes related to mitochondrial function when compared to controls. Additionally, the ICP‐MS revealed increased levels of zinc, calcium and sodium in the AD OM cells in comparison to the OM cells derived from cognitively healthy subjects.ConclusionThe results implicate the role of olfactory mucosa as a site displaying early alterations related to Alzheimer’s disease.