key: cord-0952171-2ed7me5o
authors: Quincozes‐Santos, André; da Rosa, Rafael L.; Bobermin, Larissa D.; Tureta, Emanuela F.; Santi, Lucélia; Beys‐da‐Silva, Walter O.
title: Association between molecular markers of COVID‐19 and Alzheimer's disease
date: 2021-10-19
journal: J Med Virol
DOI: 10.1002/jmv.27391
sha: f293fd0258ec481a9a3badf65109c901844468da
doc_id: 952171
cord_uid: 2ed7me5o

The COVID-19 pandemic has represented an exceptional health challenge since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has acute and chronic consequences. Acute events are mainly related to the respiratory tract; however, SARS-CoV-2 may affect cardiovascular system, kidneys, gut, and brain. Several studies have suggested patients with more severe systemic presentations are most affected by neurological symptoms, 1,2 while data from brain of postmortem patients show that SARS-CoV-2 has neuroinvasive properties. The outcomes in the central nervous system (CNS) may be also associated with an exacerbated inflammatory process, or cytokine storm, a well-characterized effect of COVID-19 that result from an overreaction of immune system, particularly involving the augment of interleukin 6 (IL-6). In line with this, SARS-CoV-2 may activate glial cells, thus potentially triggering chronic neuroinflammation and neurodegeneration. 3 This article is protected by copyright. All rights reserved.

To the Editor,

The COVID-19 pandemic has represented an exceptional health challenge as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has acute and chronic consequences. Acute events are mainly related to the respiratory tract; however, SARS-CoV-2 may affect the cardiovascular system, kidneys, gut, and brain. Several studies have suggested patients with more severe systemic presentations are most affected by neurological symptoms, 1,2 while data from brains of postmortem patients show that SARS-CoV-2 has neuroinvasive properties. The outcomes in the central nervous system (CNS) may be also associated with an exacerbated inflammatory process, or cytokine storm, a well-characterized effect of COVID-19 that results from an overreaction of the immune system, particularly involving the augment of interleukin 6 (IL-6). In line with this, SARS-CoV-2 may activate glial cells, thus potentially triggering chronic neuroinflammation and neurodegeneration. 3 LGALS3 promotes Aβ oligomerization and toxicity in AD animal models, and it is increased in AD patients. 9 In contrast, membrane metalloendopeptidase and ABCB1, which participate in the degradation and clearance of Aβ, 8 were downregulated.

Regarding CHRNA7, it was upregulated and has been increased in both neurons and astrocytes. 8 We also identified upregulation of IGFBP3 and JAK2. IGFBP3

can act as an inflammatory mediator and is highly increased in AD brains, in addition to possibly contribute to tau phosphorylation and cell death induced by Aβ, 10 while the JAK2/STAT3 pathway can modulate inflammatory responses and glial activation, indirectly regulating Aβ deposition and cognitive decline. CTSL, a proteinase that may be involved in immune system responses, was also upregulated and, interestingly, it is necessary for entry of the SARS-CoV-2 into the cell. 11 Although interferon-gamma participates in the inflammatory response, we found a downregulation of this gene, that can increase microglial activation and proinflammatory cytokines, but it also diminished phospho-tau pathology and increased neurogenesis in an animal model of AD. 12 Other genes related to immune pathways and that represent possible biomarkers for AD were also differentially expressed. AD is additionally linked to glucose and cholesterol metabolism, which presents an upregulation of genes related to glycolysis and synthesis and endocytosis of cholesterol. Moreover, we identified changes in the expression of genes that may be associated with responses to cellular energy levels and cellular stress, as well as neuronal cell death. Importantly, all these alterations can be found in both EOAD and LOAD. 13 In summary, our data provided inputs/citations of biomarkers, gene expression, and posttranslational modifications,

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