Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease
Abstract 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 an...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-023-01647-1 |
| _version_ | 1797451108549918720 |
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| author | Louise Reveret Manon Leclerc Vincent Emond Cyntia Tremblay Andréanne Loiselle Philippe Bourassa David A. Bennett Sébastien S. Hébert Frédéric Calon |
| author_facet | Louise Reveret Manon Leclerc Vincent Emond Cyntia Tremblay Andréanne Loiselle Philippe Bourassa David A. Bennett Sébastien S. Hébert Frédéric Calon |
| author_sort | Louise Reveret |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-09T14:50:08Z |
| format | Article |
| id | doaj.art-35a368b7de5c46d7b1fd90b978430f40 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-03-09T14:50:08Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-35a368b7de5c46d7b1fd90b978430f402023-11-26T14:32:00ZengBMCActa Neuropathologica Communications2051-59602023-10-0111111710.1186/s40478-023-01647-1Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s diseaseLouise Reveret0Manon Leclerc1Vincent Emond2Cyntia Tremblay3Andréanne Loiselle4Philippe Bourassa5David A. Bennett6Sébastien S. Hébert7Frédéric Calon8Faculty of Pharmacy, Laval UniversityFaculty of Pharmacy, Laval UniversityCHU de Quebec Research CenterCHU de Quebec Research CenterCHU de Quebec Research CenterFaculty of Pharmacy, Laval UniversityRush Alzheimer’s Disease Center, Rush University Medical CenterCHU de Quebec Research CenterFaculty of Pharmacy, Laval UniversityAbstract 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.https://doi.org/10.1186/s40478-023-01647-1ACE2Alzheimer’s diseaseCognitive dysfunctionBlood–brain barrierNeuropathology |
| spellingShingle | Louise Reveret Manon Leclerc Vincent Emond Cyntia Tremblay Andréanne Loiselle Philippe Bourassa David A. Bennett Sébastien S. Hébert Frédéric Calon Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease Acta Neuropathologica Communications ACE2 Alzheimer’s disease Cognitive dysfunction Blood–brain barrier Neuropathology |
| 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 | ACE2 Alzheimer’s disease Cognitive dysfunction Blood–brain barrier Neuropathology |
| url | https://doi.org/10.1186/s40478-023-01647-1 |
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