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Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2 : preliminary findings

Granholm, Ann-Charlotte E ; Englund, Elisabet LU orcid ; Gilmore, Anah ; Head, Elizabeth ; Yong, William H ; Perez, Sylvia E ; Guzman, Samuel J ; Hamlett, Eric D and Mufson, Elliott J (2024) In Acta Neuropathologica 147. p.1-21
Abstract

The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of... (More)

The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aβ deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Down Syndrome/pathology, Alzheimer Disease/pathology, COVID-19/pathology, Male, Female, Aged, Middle Aged, Brain/pathology, Aged, 80 and over, Astrocytes/pathology, Amyloid beta-Peptides/metabolism, SARS-CoV-2/pathogenicity, Microglia/pathology, Adult, tau Proteins/metabolism
in
Acta Neuropathologica
volume
147
article number
92
pages
1 - 21
publisher
Springer
external identifiers
  • pmid:38801558
ISSN
1432-0533
DOI
10.1007/s00401-024-02743-9
language
English
LU publication?
yes
additional info
© 2024. The Author(s).
id
5b82e49d-ed8f-48f5-8817-b94366f09825
date added to LUP
2024-05-28 09:55:23
date last changed
2024-05-28 10:36:24
@article{5b82e49d-ed8f-48f5-8817-b94366f09825,
  abstract     = {{<p>The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aβ deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.</p>}},
  author       = {{Granholm, Ann-Charlotte E and Englund, Elisabet and Gilmore, Anah and Head, Elizabeth and Yong, William H and Perez, Sylvia E and Guzman, Samuel J and Hamlett, Eric D and Mufson, Elliott J}},
  issn         = {{1432-0533}},
  keywords     = {{Humans; Down Syndrome/pathology; Alzheimer Disease/pathology; COVID-19/pathology; Male; Female; Aged; Middle Aged; Brain/pathology; Aged, 80 and over; Astrocytes/pathology; Amyloid beta-Peptides/metabolism; SARS-CoV-2/pathogenicity; Microglia/pathology; Adult; tau Proteins/metabolism}},
  language     = {{eng}},
  month        = {{05}},
  pages        = {{1--21}},
  publisher    = {{Springer}},
  series       = {{Acta Neuropathologica}},
  title        = {{Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2 : preliminary findings}},
  url          = {{http://dx.doi.org/10.1007/s00401-024-02743-9}},
  doi          = {{10.1007/s00401-024-02743-9}},
  volume       = {{147}},
  year         = {{2024}},
}