P3–074: Regional differences in perivascular drainage of beta‐amyloid from the aging mouse brain
Bibliographic record
Abstract
The development of cerebral amyloid angiopathy (CAA), the deposition ofamyloid-β (Aβ) in the walls of cerebral blood vessels, is associated with failure of elimination of Aβfrom the brain via drainage along perivascular basement membranes. For reasons that are as yet unknown, CAA is observed predominantly in the parietal and occipital cortices, whereas vessels in the basal ganglia and thalamus are rarely affected. In this study we tested the hypothesis that regional variation in vascular basement membranes and perivascular drainage of Aβ contribute in an age-related manner to the different regional patterns of CAA in the mouse brain. Brains from 2, 7- and 22-month-old C57Bl/6 mice were collected and dissected for cerebral cortex, hippocampus, striatum and thalamus. Basement membrane thickness was assessed by quantitative electron microscopy in capillaries from each brain region. Individual basement membrane protein levels were assessed by Western blotting and immunocytochemistry. Perivascular drainage of human A β 40 was evaluated by stereotaxic injection into the left hippocampus or thalamus of 7- and 20-month old C57Bl/6 mice. The number of Aβ-positive vessels was quantified in the cortex, hippocampus, striatum and thalamus, at 200 μm intervals up to 1000 μm away from the injection site. Significant age-related thickening of capillary basement membranes was noted in the cerebral cortex, hippocampus, and thalamus, but not in the striatum. A significant decrease in collagen IV, laminin and nidogen 2 was noted in the cortex of 23-month-old mice compared with young and adult animals. In contrast, levels of fibronectin and perlecan were significant upregulated in all brain areas of aged mice. Analysis of perivascular drainage of A β 40 from the hippocampus and thalamus of 7- and 20-month-old mice showed that the maximal number of A β -containing arteries was observed in anterior sections of the ipsilateral hippocampus, regardless of the site of injection. With age, the peak number of arteries containing A β was decreased following injection into the hippocampus, but not when injected into the thalamus. These results suggest that the topographic distribution of CAA is due in part to regional differences in the efficiency of perivascular drainage from the aging brain along cerebrovascular basement membranes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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 source (direct Gemma or distilled Codex), 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".