Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2 : preliminary findings
(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.
(Less)
- author
- Granholm, Ann-Charlotte E
; Englund, Elisabet
LU
; Gilmore, Anah ; Head, Elizabeth ; Yong, William H ; Perez, Sylvia E ; Guzman, Samuel J ; Hamlett, Eric D and Mufson, Elliott J
- organization
- publishing date
- 2024-05-27
- 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}}, }