Potential implications of endogenous aldehydes in β‐amyloid misfolding, oligomerization and fibrillogenesis
Bibliographic record
Abstract
Aldehydes are capable of inducing protein cross-linkage. An increase in aldehydes has been found in Alzheimer's disease. Formaldehyde and methylglyoxal are produced via deamination of, respectively, methylamine and aminoacetone catalyzed by semicarbazide-sensitive amine oxidase (SSAO, EC 1.4.3.6. The enzyme is located on the outer surface of the vasculature, where amyloidosis is often initiated. A high SSAO level has been identified as a risk factor for vascular disorders. Serum SSAO activity has been found to be increased in Alzheimer's patients. Malondialdehyde and 4-hydroxynonenal are derived from lipid peroxidation under oxidative stress, which is also associated with Alzheimer's disease. Aldehydes may potentially play roles in beta-amyloid aggregation related to the pathology of Alzheimer's disease. In the present study, thioflavin-T fluorometry, dynamic light scattering, circular dichroism spectroscopy and atomic force microscopy were employed to reveal the effect of endogenous aldehydes on beta-amyloid at different stages, i.e. beta-sheet formation, oligomerization and fibrillogenesis. Formaldehyde, methylglyoxal and malondialdehyde and, to a lesser extent, 4-hydroxynonenal are not only capable of enhancing the rate of formation of beta-amyloid beta-sheets, oligomers and protofibrils but also of increasing the size of the aggregates. The possible relevance to Alzheimer's disease of the effects of these aldehydes on beta-amyloid deposition is discussed.
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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 | 0.000 | 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 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".