Summary: Researchers uncovered how Alzheimers Disease (AD) impacts COVID-19 outcomes through changes in the olfactory mucosal cells. Their study focused on individuals with AD who experienced exacerbated COVID-19 symptoms.

Using an advanced 3D in vitro model of the olfactory mucosa, the research revealed that while initial infection rates were similar between healthy individuals and those with AD, the latter showed altered gene activities post-infection, indicating heightened oxidative stress and immune response changes.

This study provides crucial insights into the interplay between COVID-19 and AD, particularly through the olfactory system.

Key Facts:

Source: University of Eastern Finland

A new study identifies alterations in the transcriptomic signatures in human olfactory mucosal cells of individuals with Alzheimers disease following SARS-CoV-2 infection, potentially contributing to exacerbated COVID-19 outcomes.

The study was conducted at the University of Eastern Finland in collaboration with the University of Helsinki and published inJournal of Neuroinflammation.

The study was prompted by concerns about the impact of COVID-19 on individuals with pre-existing conditions such as Alzheimers disease (AD). Olfactory dysfunction, characterized by an impaired sense of smell, is commonly associated with COVID-19 and is also observed in persons with AD.

Exploring the olfactory mucosa as a direct interface between the external environment and the brain, the research aimed to investigate the interaction between SARS-CoV-2 infection and AD within the olfactory mucosa , assessing the potential for this tissue to serve as a plausible entry route for the virus into the brain.

Employing an innovative 3D in vitro model of the olfactory mucosa, the study utilized primary cells obtained from voluntary donors, including both cognitively healthy individuals and those diagnosed with AD.

These cells were cultivated at the air-liquid interface (ALI), a technique providing a controlled environment that closely mimics physiological conditions. The collection of olfactory mucosal biopsies was conducted collaboratively with Kuopio University Hospital.

This multidisciplinary research integrated expertise from molecular and cellular biology, neurology, and virology to investigate the effects of various SARS-CoV-2 variants on the olfactory mucosa.

Distinct immune responses after infection between AD patients and healthy individuals

Contrary to expectations, cells derived from healthy individuals and those with AD exhibited comparable susceptibility to infection by SARS-CoV-2 virus, indicating no significant difference in initial infection rates between the two groups.

However, a significant contrast emerged in the gene activity of infected cells from individuals with AD. Their cells displayed heightened oxidative stress, altered immune responses, and substantial changes in genes related to olfaction when compared to olfactory mucosal cells from cognitively healthy individuals.

The results suggest a plausible scenario where individuals affected by AD might face potentially more severe COVID-19 outcomes due to pre-existing inflammation in the olfactory mucosa, says Ali Shahbaz, a doctoral researcher in Professor Katja Kanninens research group at the University of Eastern Finland and the first author of the study.

The present study represents a pivotal advancement in understanding the intricate interplay between COVID-19 and AD.

Funding: The study was funded by the Academy of Finland.

Author: Ulla Kaltiala Source: University of Eastern Finland Contact: Ulla Kaltiala University of Eastern Finland Image: The image is credited to Neuroscience News

Original Research: Open access. Human-derived airliquid interface cultures decipher Alzheimers diseaseSARS-CoV-2 crosstalk in the olfactory mucosa by Katja Kanninen et al. Journal of Neuroinflammation

Abstract

Human-derived airliquid interface cultures decipher Alzheimers diseaseSARS-CoV-2 crosstalk in the olfactory mucosa

The neurological effects of the coronavirus disease of 2019 (COVID-19) raise concerns about potential long-term consequences, such as an increased risk of Alzheimers disease (AD). Neuroinflammation and other AD-associated pathologies are also suggested to increase the risk of serious SARS-CoV-2 infection. Anosmia is a common neurological symptom reported in COVID-19 and in early AD. The olfactory mucosa (OM) is important for the perception of smell and a proposed site of viral entry to the brain. However, little is known about SARS-CoV-2 infection at the OM of individuals with AD.

To address this gap, we established a 3D in vitro model of the OM from primary cells derived from cognitively healthy and AD individuals. We cultured the cells at the airliquid interface (ALI) to study SARS-CoV-2 infection under controlled experimental conditions. Primary OM cells in ALI expressed angiotensin-converting enzyme 2 (ACE-2), neuropilin-1 (NRP-1), and several other known SARS-CoV-2 receptor and were highly vulnerable to infection. Infection was determined by secreted viral RNA content and confirmed with SARS-CoV-2 nucleocapsid protein (NP) in the infected cells by immunocytochemistry. Differential responses of healthy and AD individuals-derived OM cells to SARS-CoV-2 were determined by RNA sequencing.

Results indicate that cells derived from cognitively healthy donors and individuals with AD do not differ in susceptibility to infection with the wild-type SARS-CoV-2 virus. However, transcriptomic signatures in cells from individuals with AD are highly distinct. Specifically, the cells from AD patients that were infected with the virus showed increased levels of oxidative stress, desensitized inflammation and immune responses, and alterations to genes associated with olfaction. These results imply that individuals with AD may be at a greater risk of experiencing severe outcomes from the infection, potentially driven by pre-existing neuroinflammation.

The study sheds light on the interplay between AD pathology and SARS-CoV-2 infection. Altered transcriptomic signatures in AD cells may contribute to unique symptoms and a more severe disease course, with a notable involvement of neuroinflammation. Furthermore, the research emphasizes the need for targeted interventions to enhance outcomes for AD patients with viral infection. The study is crucial to better comprehend the relationship between AD, COVID-19, and anosmia. It highlights the importance of ongoing research to develop more effective treatments for those at high risk of severe SARS-CoV-2 infection.

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Alzheimers Alters COVID-19 Response in Olfactory Cells - Neuroscience News