Amyloid-β-dependent compromise of microvascular structure and function in a model of Alzheimer’s disease
Bibliographic record
Abstract
The majority of patients with Alzheimer's disease have cerebral amyloid angiopathy, thus showing deposition of amyloid-β peptides in the walls of leptomeningeal and cortical arterioles. These deposits are believed to result from impaired clearance of parenchymal amyloid-β peptides. In the current work, we examined the changes in cortical microvascular structure and function in situ in TgCRND8, a transgenic mouse model of Alzheimer's disease. In contrast to venules, cortical arterioles were shown to increase in tortuosity and decrease in calibre with amyloid-β peptide accumulation. These structural changes were accompanied by progressive functional compromise, reflected in higher dispersion of microvascular network transit times, elongation of the transit times, and impaired microvascular reactivity to hypercapnia in the transgenic mice. Moreover, inhibition of amyloid-β peptide oligomerization and fibrillization via post-weaning administration of scyllo-inositol, a naturally occurring stereoisomer of myo-inositol, rescued both structural and functional impairment of the cortical microvasculature in this Alzheimer's disease model. These results demonstrate that microvascular impairment is directly correlated with amyloid-β accumulation and highlight the importance of targeting cerebrovascular amyloid angiopathy clearance for effective diagnosis, monitoring of disease progression and treatment of Alzheimer's 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".