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Record W4387258701 · doi:10.1186/s40478-023-01647-1

Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease

2023· article· en· W4387258701 on OpenAlexafffund
Louise Réveret, Manon Leclerc, Vincent Émond, Cyntia Tremblay, Andréanne Loiselle, Philippe Bourassa, David A. Bennett, Sébastien S. Hébert, Frédéric Calon

Bibliographic record

VenueActa Neuropathologica Communications · 2023
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsUniversité LavalCentre hospitalier universitaire de Québec
FundersFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchNational Institute for Health and Care ResearchConsortium canadien en neurodégénérescence associée au vieillissementNational Institute on AgingUniversité Laval
KeywordsNeuropathologyAngiotensin-converting enzyme 2Internal medicineEndocrinologyMedicineHuman brainNeurologyReceptorAlzheimer's diseaseRenin–angiotensin systemDiseaseBiologyNeuroscienceCoronavirus disease 2019 (COVID-19)Blood pressure

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.215
Threshold uncertainty score0.411

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.163
GPT teacher head0.382
Teacher spread0.218 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations40
Published2023
Admission routes2
Has abstractyes

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