Recapitulation of pathophysiological features of AD in SARS-CoV-2 infected subjects
- Icahn School of Medicine at Mount Sinai, United States
- Tulane National Primate Research Center, United States
Abstract
Infection with the etiological agent of COVID-19, SARS-CoV-2, appears capable of impacting cognition, which some patients with Post-acute Sequelae of SARS-CoV-2 (PASC). To evaluate neuro-pathophysiological consequences of SARS-CoV-2 infection, we examine transcriptional and cellular signatures in the Broadman area 9 (BA9) of the frontal cortex and the hippocampal formation (HF) in SARS-CoV-2, Alzheimer's disease (AD) and SARS-CoV-2 infected AD individuals, compared to age- and gender-matched neurological cases. Here we show similar alterations of neuroinflammation and blood-brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2 infected AD individuals. Distribution of microglial changes reflected by the increase of Iba-1 reveal nodular morphological alterations in SARS-CoV-2 infected AD individuals. Similarly, HIF-1α is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status. The finding may help to inform decision-making regarding therapeutic treatments in patients with neuro-PASC, especially those at increased risk of developing AD.
Data availability
The authors declare that the data supporting the findings of this study are available within the paper and its supplementary information files. The raw data discussed in this publication are accessible through NCBI's Gene Expression Ominubus (GEO).
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Recapitulation of pathophysiological features of AD in SARS-CoV-2 -infected subjectsNCBI Gene Expression Omnibus, GSE236562.
Article and author information
Author details
Giulio Maria Pasinetti
Funding
No external funding was received for this work.
Reviewing Editor
- Laura L Colgin, University of Texas at Austin, United States
Ethics
Human subjects: While no living humans or animals were used for these studies, we performed studies using human postmortem tissue in accordance with IRB-approved guidelines and regulations at Mount Sinai.
Version history
- Preprint posted: November 23, 2022 (view preprint)
- Received: January 20, 2023
- Accepted: June 22, 2023
- Accepted Manuscript published: July 7, 2023 (version 1)
- Version of Record published: July 21, 2023 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Recapitulation of pathophysiological features of AD in SARS-CoV-2 infected subjects
eLife 12:e86333.
https://doi.org/10.7554/eLife.86333
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