Peripheral and total circulating extracellular vesicle levels of advanced glycation end‐products and RAGEs as possible biomarkers for mild cognitive impairment and Alzheimer's patients
Bibliographic record
Abstract
Abstract Background Advanced glycation end‐products (AGEs), their precursors methylglyoxal (MG), glyoxal (GO) and their receptors RAGEs are known to be involved in the pathophysiology of Alzheimer’s disease (AD). The aim of our study was to evidence the presence of RAGEs and glyoxalase‐1 (GLO‐1), the main enzyme involved in the degradation of MG, in the circulating extracellular vesicles (pEVs) from control subjects, mild cognitive impairment (MCI) and AD patients. Method EVs were isolated from plasma of control, MCI and AD subjects at different stages of the disease (early , moderate and severe). Their size, shape and density were characterized. The presence of EVs specific proteins TSG101, CD63, GAPDH were confirmed by Western Blot. MG and GO levels in serum were determined by HPLC. In addition, serum Pentosidine and CML levels were determined by competitive ELISA. Result Our data showed lower levels of RAGE in pEVs from MCI, early and moderate stage of AD patients as compared to the severe stage of AD patients. GLO‐1 levels in pEVs were significantly decreased in early AD as compared to controls and MCI. Interestingly, RAGEs and GLO‐1 levels in pEVs were correlated with the clinical cognitive scores. MG and GO levels in serum were higher in MCI and receiver‐operating characteristic curves analysis showed that serum MG levels have higher sensitivity to differentiate MCI from controls but not from AD. Meanwhile, serum GO levels differentiate MCI from control and AD groups. The levels of CML in albumin‐free serum proteins were higher in the early stage of AD while, the levels of pentosidine remained unchanged and were negatively correlated with the clinical cognitive scores MMSE and MoCA. In contrast, the levels of N‐(1‐carboxymethyl)‐L‐lysine in pEVs were lower in the moderate stage of AD. Conclusion Levels of some AGEs and RAGEs in serum and in total circulating EVs could be used as possible biomarkers for MCI and AD. This work was supported by the Chaire Louise & André on Alzheimer’s disease, Foundation Armand‐Frappier (CR) and CIHR grant (TF).
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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 | 0.001 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".