Alan Mackay-Sim, Australia
Griffith University Griffith Institute for Drug DiscoveryAuthor Of 1 Presentation
DISEASE SPECIFIC ALTERATIONS IN THE OLFACTORY MUCOSA OF PATIENTS WITH ALZHEIMER’S DISEASE
Abstract
Aims
The sense of smell is orchestrated by the olfactory mucosa in the upper nasal cavity. Cells of the olfactory mucosa are known to be altered in certain neurodegenerative conditions but have not been well characterized in Alzheimer’s Disease. This is surprising given that loss of olfaction is one of the earliest symptoms of the disease. Here we report the use of olfactory mucosa cells obtained from living biopsy donors as a research model for Alzheimer’s Disease.
Methods
For the first time we have applied single-cell RNA sequencing of olfactory mucosa cells obtained from cognitively normal individuals and persons with Alzheimer’s Disease to provide subtle delineation of cellular heterogeneity in olfactory mucosa cells, revealing the existence of potential markers and key factors contributing to the disease.
Results
The single-cell RNA sequencing approach elucidated the cellular makeup of individual olfactory mucosa cells. It uncovered a total of 1766 annotated genes, of which 136 were differentially expressed in persons with Alzheimer’s Disease. 62 % of the altered genes were up regulated while the expression of 38 % of the genes were reduced in persons with Alzheimer’s Disease compared to cognitively normal individuals. Functional testing of beta-amyloid production revealed distinct alterations of the cells derived from persons with Alzheimer’s Disease as the levels of tau protein and secreted cytokines were unaltered between the study groups.
Conclusions
Taken together, our results support the utilization of olfactory mucosa cells as a research model, which holds promise for detailed understanding of disease mechanisms and discovery of biomarkers for Alzheimer’s Disease.