Vascular and extravascular localization of Aβ in Alzheimer’s retina
Bibliographic record
Abstract
Abstract Background Recent in vivo and ex vivo studies have demonstrated retinal vasculopathy may be associated with Alzheimer’s disease (AD). We investigated amyloid beta (Ab) localization relative to vessels in wholemount retinas from AD and control donors. We specifically tested whether extravascular retinal Ab aggregated toward vessels and whether the Ab localization pattern differed between the AD and control retinas. Method From 15 AD donors and 10 age‐matched controls, free‐floating punches were taken in the foveal, peri‐foveal, and mid‐peripheral temporal, superior, and inferior neuro‐retina. Immunohistochemistry was performed for Ab (6F/3D, 12F4) with secondary antibodies tagged with Cy3. The punches were imaged at 543‐nm using Zeiss LSM 510 confocal microscope focused at the ganglion cell layer in four non‐overlapping 450mm x 450mm images. Blind raters segmented the images into intravascular and extravascular regions excluding cell bodies and artefacts. Quantitative analysis was performed as follows: Ab reactivity was detected pixel‐wise by intensity thresholding, and the total vessel area, raw and normalized intra‐ and extravascular Ab load, and vessel proximity of extravascular Ab were computed. Result Out of 452 images 272 contained visible vessels. Total vessel area was lower in the AD retinas in the superior region (p = 0.004). There was no group difference in Ab load except in the temporal intravascular region (p = 0.007); however, intravascular Ab signal may be due to blood artefacts and requires caution in interpretation. Aggregation of Ab near vessels was tested by comparing the vessel proximity of extravascular Ab‐positive pixels against that of all other pixels in the extravascular region. Extravascular Ab were located significantly closer to the vessels than the background in the control retinas in the peri‐fovea (p = 0.0023) and temporal (p = 0.001) regions, but this was not observed in AD retinas. Conclusion With our previous study on intracellular retinal Ab, the current study suggests that Ab deposition pattern in the retina is specific in spatial regions (eg. temporal, superior) and anatomical regions (eg. intracellular, intravascular). The non‐specificity of Ab localization relative to the vessels in AD may indicate compromised Ab clearance via retinal vasculature.
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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 | 0.001 |
| 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".