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Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease
Cognitive decline due to Alzheimer’s disease (AD) is frequent in the geriatric population, which has been disproportionately affected by the COVID-19 pandemic. In this study, we investigated the levels of angiotensin-converting enzyme 2 (ACE2), a regulator of the renin-angiotensin system and the mai...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10544218/ https://www.ncbi.nlm.nih.gov/pubmed/37784209 http://dx.doi.org/10.1186/s40478-023-01647-1 |
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author | Reveret, Louise Leclerc, Manon Emond, Vincent Tremblay, Cyntia Loiselle, Andréanne Bourassa, Philippe Bennett, David A. Hébert, Sébastien S. Calon, Frédéric |
author_facet | Reveret, Louise Leclerc, Manon Emond, Vincent Tremblay, Cyntia Loiselle, Andréanne Bourassa, Philippe Bennett, David A. Hébert, Sébastien S. Calon, Frédéric |
author_sort | Reveret, Louise |
collection | PubMed |
description | Cognitive decline due to Alzheimer’s disease (AD) is frequent in the geriatric population, which has been disproportionately affected by the COVID-19 pandemic. In this study, we investigated the levels of angiotensin-converting enzyme 2 (ACE2), a regulator of the renin-angiotensin system and the main entry receptor of SARS-CoV-2 in host cells, in postmortem parietal cortex samples from two independent AD cohorts, totalling 142 persons. Higher concentrations of ACE2 protein (p < 0.01) and mRNA (p < 0.01) were found in individuals with a neuropathological diagnosis of AD compared to age-matched healthy control subjects. Brain levels of soluble ACE2 were inversely associated with cognitive scores (p = 0.02) and markers of pericytes (PDGFRβ, p = 0.02 and ANPEP, p = 0.007), but positively correlated with concentrations of soluble amyloid-β peptides (Aβ) (p = 0.01) and insoluble phospho-tau (S396/404, p = 0.002). However, no significant differences in ACE2 were observed in the 3xTg-AD mouse model of tau and Aβ neuropathology. Results from immunofluorescence and Western blots showed that ACE2 protein is predominantly localized in microvessels in the mouse brain whereas it is more frequently found in neurons in the human brain. The present data suggest that higher levels of soluble ACE2 in the human brain may contribute to AD, but their role in CNS infection by SARS-CoV-2 remains unclear. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-023-01647-1. |
format | Online Article Text |
id | pubmed-10544218 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-105442182023-10-03 Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease Reveret, Louise Leclerc, Manon Emond, Vincent Tremblay, Cyntia Loiselle, Andréanne Bourassa, Philippe Bennett, David A. Hébert, Sébastien S. Calon, Frédéric Acta Neuropathol Commun Research Cognitive decline due to Alzheimer’s disease (AD) is frequent in the geriatric population, which has been disproportionately affected by the COVID-19 pandemic. In this study, we investigated the levels of angiotensin-converting enzyme 2 (ACE2), a regulator of the renin-angiotensin system and the main entry receptor of SARS-CoV-2 in host cells, in postmortem parietal cortex samples from two independent AD cohorts, totalling 142 persons. Higher concentrations of ACE2 protein (p < 0.01) and mRNA (p < 0.01) were found in individuals with a neuropathological diagnosis of AD compared to age-matched healthy control subjects. Brain levels of soluble ACE2 were inversely associated with cognitive scores (p = 0.02) and markers of pericytes (PDGFRβ, p = 0.02 and ANPEP, p = 0.007), but positively correlated with concentrations of soluble amyloid-β peptides (Aβ) (p = 0.01) and insoluble phospho-tau (S396/404, p = 0.002). However, no significant differences in ACE2 were observed in the 3xTg-AD mouse model of tau and Aβ neuropathology. Results from immunofluorescence and Western blots showed that ACE2 protein is predominantly localized in microvessels in the mouse brain whereas it is more frequently found in neurons in the human brain. The present data suggest that higher levels of soluble ACE2 in the human brain may contribute to AD, but their role in CNS infection by SARS-CoV-2 remains unclear. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-023-01647-1. BioMed Central 2023-10-02 /pmc/articles/PMC10544218/ /pubmed/37784209 http://dx.doi.org/10.1186/s40478-023-01647-1 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Reveret, Louise Leclerc, Manon Emond, Vincent Tremblay, Cyntia Loiselle, Andréanne Bourassa, Philippe Bennett, David A. Hébert, Sébastien S. Calon, Frédéric Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease |
title | Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease |
title_full | Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease |
title_fullStr | Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease |
title_full_unstemmed | Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease |
title_short | Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease |
title_sort | higher angiotensin-converting enzyme 2 (ace2) levels in the brain of individuals with alzheimer’s disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10544218/ https://www.ncbi.nlm.nih.gov/pubmed/37784209 http://dx.doi.org/10.1186/s40478-023-01647-1 |
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