[P1–116]: THE RELATIONSHIP BETWEEN AMYLOID IN THE RETINA AND A BRAIN‐BASED POST‐MORTEM DIAGNOSIS OF ALZHEIMER's DISEASE
Bibliographic record
Abstract
We have previously shown that amyloid deposits in the neural retina in human are a biomarker of Alzheimer's disease (AD) and that there is evidence that they are amyloid beta (Aβ). Here we compare the occurrence of amyloid in post-mortem human retina with brain pathology at the time of death. Eyes and brains were obtained from 16 donors with a variety of neurological disorders, including 13 with AD as a primary or secondary diagnosis. One eye per subject was fixed in 10% formalin for 24 hours and then switched to 0.1% formalin in PBS. The retina was stained with 0.1% Thioflavin-S and counterstained with DAPI, flat mounted, and imaged in fluorescence microscopy and polarimetry. Brains were examined by a neuropathologist and the severity of AD pathology determined according to NIA guidelines based on assessment of neuritic senile plaque numbers (CERAD), anatomical distribution of Aβ deposits (Thal phase, TP), anatomical distribution of tau-immunoreactive neurofibrillary tangles (Braak stage, BS), and a cumulative score of the severity of AD pathology (CSS). The number of deposits found in the anterior layers of the retina with a signal in both fluorescence and polarimetry were then compared to these measures of AD brain pathology. Retinal amyloid deposits showed contrast in polarized light, similar to that of pure Aβ deposits. Amyloid occurred in the retina with 100% sensitivity for AD. There were no retinal deposits in the 2 individuals with no AD brain pathology (CSS=0). The Spearman's rhos (ρ) between number of retinal amyloid deposits and CSS as well as TP and BS measures of AD brain pathology were significant. Gamma (γ) showed moderate relationships between amyloid deposits with CSS and TP (γ=0.71 and 0.70); BS (γ=0.62); and CERAD (γ =0.51). Most amyloid deposits in the retina would be large enough to be resolved in vivo. The number of retinal amyloid deposits correlates both to a cumulative score of AD brain pathology and to other measures of brain AD pathology, but not robustly to neuritic plaques. Thus in vivo retinal imaging of amyloid deposits, including polarization imaging, is a promising window onto AD brain pathology. An amyloid deposit observed in an anterior layer of the retina. On the left, fluorescence from Thioflavin S is visible. On the right, the deposit is observed in cross circular polarization. The average number of amyloid deposits in the retina versus the cumulative score of severity of AD pathology in the brain (CSS). As the severity of AD brain pathology increases, so do the number of amyloid deposits in the brain. The values of Spearman's rho and Gamma are given for each of the measures of AD brain pathology. The critical value for the Spearman's rho is 0.503.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".