Pleiotropic Benefits of the Angiotensin Receptor Blocker Candesartan in a Mouse Model of Alzheimer Disease
Bibliographic record
Abstract
The angiotensin receptor blocker losartan mitigated cerebrovascular and cognitive deficits in mouse models of Alzheimer disease, in line with some clinical evidence of reduced onset and progression to Alzheimer disease. We investigated whether these benefits apply to another angiotensin receptor blocker, namely candesartan. Adult transgenic mice overexpressing a mutated form of the human APP (amyloid precursor protein) and wild-type controls were treated with vehicle or candesartan (cohort 1: 2 months, 1 mg/kg per day, osmotic subcutaneous minipumps; cohort 2: 5 months, 10 mg/kg per day in drinking water). Candesartan largely restored endothelial and smooth muscle function and reduced neuroinflammation in both cohorts, without improving sensory evoked cerebral blood flow responses. Candesartan exerted restorative effects on the reduced number of Ki67-immunopositive proliferating cells in the granule cell layer of the hippocampus but not on that of DCX (doublecortin)-positive immature granule cells, despite normalizing the length of their dendritic projections in the molecular layer. Amyloid plaque load and impaired cognitive function were unaltered by candesartan, and blood pressure was decreased in treated APP and wild-type mice. Overall, findings show that candesartan shared several advantages reported previously for losartan, but it exhibited limited cognitive benefits and stronger blood pressure lowering effects. The choice of angiotensin receptor blocker may thus be critical for therapeutic efficacy in patients with vascular diseases at high risk of developing Alzheimer disease.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".