P3‐117: Progressive Inflammatory Pathology in the Retina of Aluminum‐Fed 5XFAD Transgenic Mice
Bibliographic record
Abstract
Approximately 60 murine transgenic models for Alzheimer's disease (Tg-AD) have been developed that overexpress the 42 amino acid amyloid-beta (Aβ42) peptide in the central nervous system (CNS). These 'humanized murine Tg-AD models' have significantly expanded our understanding of the contribution of Aβ42 peptide-mediated pro-inflammatory and amyloidogenic neuropathology to the AD process. Several laboratories using different amyloid-overexpressing Tg-AD models have independently reported that the supplementation of murine Tg-AD diets and/or drinking water with aluminum (sulfate) significantly enhances Aβ42 peptide-mediated inflammatory pathology, amyloidogenesis and AD-type cognitive change compared to age-matched controls. In humans AD-type neuropathology appears to originate in the limbic system and progressively spreads into primary processing and sensory regions such as the primary visual cortex and the retina. For the first time, here we assess the propagation of Aβ42 peptide-mediated amyloidogenesis and pro-inflammatory gene expression (at the level of miRNA, mRNA and protein) in the neocortical-thalamic-retinal visual pathway of 5xFAD Tg-AD amyloid-overexpressing mice whose diets were supplemented with aluminum (sulfate). 5xFAD Tg-AD murine models, RNA sequencing, GeneChip (microRNA and mRNA), RT-PCR, LED-Northern, Western, ELISA and bioinformatics analysis. The three most significant findings were (i) in aluminum-supplemented animals, markers for inflammatory neuropathology appeared in both the brain and the retina as evidenced by an evolving presence of Aβ42 peptides; (ii) increases in Aβ42 peptide abundance in these animals were accompanied by the up-regulation of several pro-inflammatory markers including cyclooxygenase-2 (COX-2) and C-reactive protein (CRP); and (iii) that as similarly reported in other Tg-AD murine models, there was a significantly accelerated development of Aβ42-mediated inflammatory neuropathology in 5xFAD Tg-AD mice fed aluminum. Taken together the results indicate that in the 5xFAD Tg-AD model aluminum not only enhances an Aβ42-mediated inflammatory neurodegeneration in the brain but also significantly induces AD-type neuropathology in anatomically-linked primary sensory areas that involve the acquisition and processing of visual signals.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".