Recapitulation of pathophysiological features of AD in SARS-CoV-2 infected subjects

  1. Elizabeth Griggs
  2. Kyle Trageser
  3. Sean Naughton
  4. Eun-Jeong Yang
  5. Brian Mathew
  6. Grace Van Hyfte
  7. Linh Hellmers
  8. Nathalie Jette
  9. Molly Estill
  10. Li Shen
  11. Tracy Fischer
  12. Giulio Maria Pasinetti  Is a corresponding author
  1. Icahn School of Medicine at Mount Sinai, United States
  2. 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).

The following data sets were generated

Article and author information

Author details

  1. Elizabeth Griggs

    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  2. Kyle Trageser

    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  3. Sean Naughton

    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  4. Eun-Jeong Yang

    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  5. Brian Mathew

    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  6. Grace Van Hyfte

    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  7. Linh Hellmers

    Tulane National Primate Research Center, Covington, United States
    Competing interests
    No competing interests declared.
  8. Nathalie Jette

    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    Nathalie Jette, receives grant funding paid to her institution from NINDS (NIH U24NS107201, NIH IU54NS100064, 3R01CA202911-05S1, R21NS122389, R01HL161847). Some of these grants are COVID-19 related but focus on the neuroimaging findings. The other authors declare that they have no conflict of interest with the contents of this article..
  9. Molly Estill

    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  10. Li Shen

    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  11. Tracy Fischer

    Tulane National Primate Research Center, Covington, United States
    Competing interests
    No competing interests declared.
  12. Giulio Maria Pasinetti

    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States
    For correspondence
    giulio.pasinetti@mssm.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1524-5196

Funding

No external funding was received for this work.

Reviewing Editor

  1. 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

  1. Preprint posted: November 23, 2022 (view preprint)
  2. Received: January 20, 2023
  3. Accepted: June 22, 2023
  4. Accepted Manuscript published: July 7, 2023 (version 1)
  5. 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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  1. Elizabeth Griggs
  2. Kyle Trageser
  3. Sean Naughton
  4. Eun-Jeong Yang
  5. Brian Mathew
  6. Grace Van Hyfte
  7. Linh Hellmers
  8. Nathalie Jette
  9. Molly Estill
  10. Li Shen
  11. Tracy Fischer
  12. Giulio Maria Pasinetti
(2023)
Recapitulation of pathophysiological features of AD in SARS-CoV-2 infected subjects
eLife 12:e86333.
https://doi.org/10.7554/eLife.86333

Share this article

https://doi.org/10.7554/eLife.86333

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