Decoding amyloid beta clearance systems at inner blood–retina barrier using three‐dimensional ex vivo retinal imaging in Alzheimer's disease
Bibliographic record
Abstract
INTRODUCTION: Impaired amyloid beta (Aβ) clearance contributes to sporadic Alzheimer's disease (AD). This study investigated retinal Aβ clearance involving neuronal, glial, and vascular interactions at the inner blood-retina barrier (iBRB), a functional analog of the blood-brain barrier (BBB). METHODS: Retinal wholemounts from AD donors and controls were analyzed alongside transgenic amyloid precursor protein/presenilin 1 (APP-PS1) and non-carrier control mouse retinal cross-sections using three- and two-dimensional ex vivo imaging. RESULTS: AD neuroretinas displayed increased larger Aβ42 deposits, microglial elongation, and substantial reductions in macroglial support and water channel expression. The uptake of soluble Aβ oligomers (SAβOs) by peripheral macrophage-like, Aβ-binding myeloid lineage cells was also diminished. In APP-PS1 mice, elevated glia levels, alongside increased APP/Aβ expression, suggest gliosis and failures in clearance processes with disease progression. DISCUSSION: Ex vivo three-dimensional retinal imaging at the iBRB provides novel insights into Aβ clearance in AD, which is difficult to replicate in ex vivo brain studies at the BBB. HIGHLIGHTS: Impaired clearance mechanisms play a key role in sporadic AD. The iBRB serves as a functional analog to the BBB. At the iBRB, the glymphatic system and microglial phagocytosis help mitigate Aβ burden. Peripheral macrophage-like myeloid lineage cells may aid SAβO clearance. The imaging plane (surface vs cross-section) may affect AD pathogenesis findings.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".