Abstract
Alzheimer’s disease (AD) is characterized by the deposition of amyloid-beta (Aβ) plaques from improper amyloid-beta precursor protein (APP) cleavage. Following studies of inflammation caused by coronavirus-2019 (COVID-19) infection, this study investigated the impact of COVID-19 on APP expression. A meta-analysis was conducted utilizing QIAGEN Ingenuity Pathway Analysis (IPA) to examine the link between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and the modulation of APP expression upon virus binding the Angiotensin-converting enzyme-2 (ACE2) receptor. A Core Analysis was run on the infection by severe acute respiratory syndrome (SARS) coronavirus node, which included molecules affected by SARS-CoV-2, revealing its upstream regulators. Intermediary molecules were found between the upstream regulators and ACE2 and between ACE2 and APP. Activation of the upstream regulators downregulated the expression of ACE2 with a Z-score of −1.719 (p-value = 0.086) and upregulated APP with a Z-score of 1.898 (p-value = 0.058), showing a less than 10% chance of the results occurring by chance and pointing to an inverse relationship between ACE2 and APP expression. The neuroinflammation signaling pathway was the fifth top canonical pathway involved in APP upregulation. The study results suggest that ACE2 could be downregulated by SARS-CoV-2, resulting in APP upregulation, and potentially exacerbating the onset and progression of AD.
Highlights
Received: 13 December 2021Coronavirus disease-2019 (COVID-19) is caused by the infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), whose primary target is the respiratory system
In severe acute respiratory syndrome-coronavirus (SARS-CoV-1), viral entry occurs through the interaction between the receptor-binding domain (RBD) of Supplement 1 (S1) and the PD of Angiotensin-converting enzyme-2 (ACE2), which triggers the cleavage of ACE2 by the transmembrane protease serine protease (TMPRSS) 2 and the disintegrin and metallopeptidase domain 17 (ADAM17) [2]
It is hypothesized that SARS-CoV-2 competes with Angiotensin II for binding with ACE2, causing ACE2 to be internalized upon viral
Summary
Received: 13 December 2021Coronavirus disease-2019 (COVID-19) is caused by the infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), whose primary target is the respiratory system. SARS-CoV-2 interacts with the ACE2 receptor of a host cell via its spike protein S1 subunit, which contains the receptor-binding domain (RBD) [2]. This domain interacts with the ACE2 peptidase domain (PD) to enter the host cell [2]. In severe acute respiratory syndrome-coronavirus (SARS-CoV-1), viral entry occurs through the interaction between the RBD of S1 and the PD of ACE2, which triggers the cleavage of ACE2 by the transmembrane protease serine protease (TMPRSS) 2 and the disintegrin and metallopeptidase domain 17 (ADAM17) [2]. It is hypothesized that SARS-CoV-2 competes with Angiotensin II for binding with ACE2, causing ACE2 to be internalized upon viral
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