O4‐02‐04: Selective targeting of perivascular macrophages for <i>β</i>‐amyloid clearance in cerebral amyloid angiopathy
Bibliographic record
Abstract
The majority of Alzheimer's disease (AD) cases present with cerebral amyloid angiopathy (CAA), the deposition of Aβ in cortical blood vessels and leptomeninges. Although the pathogenesis of CAA remains unknown, it has been suggested to develop in part due to impaired clearance of cerebral Aβ via perivascular interstitial fluid (ISF) drainage pathways. Perivascular macrophages are a group of innate immune cells that contribute to the formation and function of the blood brain barrier by acting as scavenger phagocytes. However, the interaction of perivascular macrophages with Aβ and the significance of this interaction in the development of CAA is unknown. The purpose of these experiments was to determine the effect of perivascular macrophage depletion and stimulation on CAA severity in the TgCRND8 animal model of AD. To deplete perivascular macrophages, 4 month-old mice received an i.c.v. injection of liposome-encapsulated clodronate into the left lateral ventricle. Perivascular macrophage turnover was induced in 5 month-old TgCRND8 mice following two i.c.v. injections of chitin. Mice were sacrificed 1 month after injection and brain tissues were processed for immunocytochemistry, immunoblotting and ELISA. Depletion of perivascular macrophages significantly increased the number of thioflavin S-positive cortical and leptomeningeal blood vessels. ELISA analyses confirmed that this increase was underscored by elevations in total vascular Aβ42 levels. Conversely, stimulation of perivascular macrophage turnover reduced cerebral CAA load, an effect that was specifically mediated by perivascular macrophages, not via clearance by microglia or astrocytes. These results highlight a function for the physiological role of perivascular macrophages in the regulation of CAA and suggest that selective targeting of perivascular macrophage activation might constitute a therapeutic strategy to clear vascular amyloid.
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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) | 0.000 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".