Vascular dementia increases levels of methylenetetrahydrofolate reductase and cystathionine β-synthase in female patients and changes gene expression of acetylcholine and glutamate clathrin-sculpted transport vesicles
Bibliographic record
Abstract
Deficiencies in one-carbon (1C) metabolism are linked to the onset of vascular dementia (VaD). Our previous work using mouse models has demonstrated that reduced dietary intake of folic acid or genetic deficiencies in 1C metabolism result in worse outcomes using a model of VaD. This study aims to provide a detailed molecular portrait of 1C metabolism within the context of VaD, shedding light on potential molecular mechanisms. In cortical post-mortem tissue from female and male VaD patients and controls we measured the folate receptor (FR) and 1C enzymes including methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), choline acetyltransferase (ChAT), acetylcholinesterase (AChE), cystathionine β-synthase (CBS), with NeuN and DAPI as markers. Additionally, spatial transcriptomics was performed on 4 samples. VaD and gender impacted levels of FR. Both male and female VaD had increased levels of ChAT. Female VaD patients had higher levels of MTHFR and CBS when compared to males. Spatial transcriptomics revealed reduced expression of the glutamate and acetylcholine clathrin-sculpted transport vesicles and increase in glutamatergic neurons. VaD is a complex disease; the results of this study demonstrate that VaD impacts levels of 1C, as well as gene expression. Dietary supplementation with 1C may be beneficial for affected patients.
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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 | 0.000 |
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".