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Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer’s Disease Patients

Authors :
Riikka Lampinen
Mohammad Feroze Fazaludeen
Simone Avesani
Tiit Örd
Elina Penttilä
Juha-Matti Lehtola
Toni Saari
Sanna Hannonen
Liudmila Saveleva
Emma Kaartinen
Francisco Fernández Acosta
Marcela Cruz-Haces
Heikki Löppönen
Alan Mackay-Sim
Minna U. Kaikkonen
Anne M. Koivisto
Tarja Malm
Anthony R. White
Rosalba Giugno
Sweelin Chew
Katja M. Kanninen
Source :
Cells, Vol 11, Iss 4, p 676 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Olfaction is orchestrated by olfactory mucosal cells located in the upper nasal cavity. Olfactory dysfunction manifests early in several neurodegenerative disorders including Alzheimer’s disease, however, disease-related alterations to the olfactory mucosal cells remain poorly described. The aim of this study was to evaluate the olfactory mucosa differences between cognitively healthy individuals and Alzheimer’s disease patients. We report increased amyloid-beta secretion in Alzheimer’s disease olfactory mucosal cells and detail cell-type-specific gene expression patterns, unveiling 240 differentially expressed disease-associated genes compared to the cognitively healthy controls, and five distinct cell populations. Overall, alterations of RNA and protein metabolism, inflammatory processes, and signal transduction were observed in multiple cell populations, suggesting their role in Alzheimer’s disease-related olfactory mucosa pathophysiology. Furthermore, the single-cell RNA-sequencing proposed alterations in gene expression of mitochondrially located genes in AD OM cells, which were verified by functional assays, demonstrating altered mitochondrial respiration and a reduction of ATP production. Our results reveal disease-related changes of olfactory mucosal cells in Alzheimer’s disease and demonstrate the utility of single-cell RNA sequencing data for investigating molecular and cellular mechanisms associated with the disease.

Details

Language :
English
ISSN :
20734409
Volume :
11
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.f37964f4ad0445378ce4d9197ff96e19
Document Type :
article
Full Text :
https://doi.org/10.3390/cells11040676