P2‐168: IMMUNOHISTOCHEMISTRY OF O‐LINKED N‐ACETYLGLUCOSAMINE TRANSFERASE (OGT) AND AUTOPHAGY MARKER LC3B IN ALZHEIMER'S DISEASE
Bibliographic record
Abstract
Early disturbances in brain glucose metabolism are characteristic in Alzheimer's Disease (AD). Modification of nuclear and cytoplasmic proteins with O-linked N-acetylglucosamine (O-GlcNAc) is dependent on glucose availability. Increased O-GlcNAc levels have been linked to protein clearance of tau and amyloid precursor protein through autophagy in mouse models. Levels of O-GlcNAc are regulated in a dynamic manner through the action of the enzyme O-linked N-acetylglucosamine transferase (OGT), which installs O-GlcNAc, and β-N-acetylglucosaminidase (OGA), which removes this modification. With disturbances in brain glucose metabolism, including in diabetes mellitus (DM) and AD, O-GlcNAc effects are modified leading to decreased clearance of proteins related to AD. However, there are inconsistent results in reported levels of OGT in AD brain tissue. We set out to evaluate OGT and autophagy in human brains with and without AD and DM with immunohistochemistry (IHC) using semiquantative methods. We examined post mortem brain tissue from patients with pathologically confirmed AD (N=20) and without AD (N=20); with half of each group also having a history of DM. IHC-staining of paraffin-embedded tissue of frontal cortex (FC), hippocampus (HC) and cerebellum (CB) was undertaken for OGT and the autophagy marker LC3-B. Intensity of staining was graded semi-quantitatively from 0 to 4. OGT staining was significantly greater (p=0.016) and there was a trend for LC3-B staining to be less (p=0.057) in the HC of AD cases compared to controls. DM did not confer any differences in the analyses. Staining intensity of OGT differed across brain regions in this study, with increases in AD in the HC but not FC or cerebellum. Despite this apparent local upregulation of OGT, there was less evidence of autophagy, suggesting a signaling impairment in AD. The discordance between HC and FC is unexplained but may be related to the relatively higher burden of AD pathology in the HC. This study adds to the evidence that OGT may be increased in AD brains.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".