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A groundbreaking study conducted by the University of Eastern Finland, in collaboration with the University of Helsinki, has uncovered significant changes in gene transcription within the olfactory mucosal cells of individuals with Alzheimer's disease (AD) following SARS-CoV-2 infection. Published in the Journal of Neuroinflammation, this research sheds light on the potential for exacerbated COVID-19 outcomes in AD patients due to these cellular alterations.

Prompted by the observed olfactory dysfunction in both COVID-19 and AD patients, the study aimed to explore the olfactory mucosa — the interface between the external environment and the brain. This exploration was to assess whether this tissue could serve as a potential entry route for the virus into the brain in AD patients.

Using a state-of-the-art 3D in vitro model of the olfactory mucosa, the research team cultivated primary cells obtained from voluntary donors, including those diagnosed with AD and cognitively healthy individuals. These cells were grown using the air-liquid interface (ALI) technique, providing conditions that closely resemble the physiological environment. The procurement of olfactory mucosal biopsies was conducted in collaboration with Kuopio University Hospital.

Intriguingly, the study found no significant difference in the susceptibility to SARS-CoV-2 infection between cells from healthy individuals and those with AD. However, infected cells from AD patients showed elevated oxidative stress and altered immune responses, along with notable changes in genes related to olfaction, compared to those from cognitively healthy individuals.

Ali Shahbaz, a doctoral researcher in Professor Katja Kanninen’s research group at the University of Eastern Finland and the first author of the study, notes, “The findings suggest that individuals with AD might experience more severe COVID-19 outcomes due to pre-existing inflammation in the olfactory mucosa.”

This study marks a significant step in understanding how COVID-19 interacts with Alzheimer's disease at the cellular level. Funded by the Academy of Finland, it combines expertise from multiple disciplines, including molecular and cellular biology, neurology, and virology, to broaden our understanding of the complex relationship between COVID-19 and neurodegenerative diseases like AD.

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