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

OOlfactory 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 Alzheimer’s disease. Here we report that Alzheimer´s disease olfactory mucosal cells 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 Alzheimer´s disease. Moreover, for the first time we provide single cell data on olfactory mucosa in Alzheimer´s disease for investigating molecular and cellular mechanisms associated with the disease.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 2 Publications

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Dataset ID	Description	Technology	Samples
EGAD00001008560	The sample AD_Library_1, AD_Library_2 and Control_Library were run on a Chromium Chip B with the Chromium Single Cell 3′ Library & Gel Bead Kit v3 kit (10x Genomics, CA, USA) . The 3’ gene expression libraries were sequenced at an approximate depth of 50,000 reads per cell using the NovaSeq 6000 S1 (Illumina, San Diego, CA, USA) flow cells. Cell Ranger v.3.0.2 was used to analyze the raw base call files. FASTQ files and raw gene-barcode matrices were generated and aligned human genome GRCh37 (hg19). The samples were integrated in R v.4.0.3 and generated Seurat objects, two related to AD samples and one to control samples, were analyzed using the Seurat package v.4.0.3 to perform downstream analysis, clustering of the cells and differential expression.		1

Publications	Citations
Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer's Disease Patients. Lampinen R, Fazaludeen MF, Avesani S, Örd T, Penttilä E, Lehtola JM, Saari T, Hannonen S, Saveleva L, Kaartinen E, Fernández Acosta F, Cruz-Haces M, Löppönen H, Mackay-Sim A, Kaikkonen MU, Koivisto AM, Malm T, White AR, Giugno R, Chew S, Kanninen KM. Cells 11: 2022 676	17
The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing. Liu Y, Tan Y, Zhang Z, Yi M, Zhu L, Peng W. Transl Neurodegener 13: 2024 7	3