Degenerative Protein Modifications in the Hippocampal Formation in Vascular Dementia
Bibliographic record
Abstract
Introduction Introduction: Ageing is associated with the pathological accumulation of damaged proteins (termed proteinopathies) that affect the cardiovascular system and the brain. Spontaneous chemical reactions such as deamidation lead to degenerative protein modifications (DPMs), including the formation of isoAsp-Gly-Arg (isoDGR) motifs. These DPMs can cause toxic gain-of-function effects, promote inflammation, and can contribute to chronic conditions such as vascular cognitive impairment and dementia. The burden of isoDGR in relation to neurofibrillary pathology however is not known across the dementias. Methods Methods: We systematically assessed isoDGR and phosphorylated-Tau (pTau) immunoreactivites in terms of densities and co-localisation frequencies across a range of dementia disorders including: post-stroke dementia, vascular dementia (VaD) and Alzheimer’s disease (AD), Mixed dementia as well as in post-stroke survivors without dementia and normal ageing control subjects (n=60; age range 73-99; male 52%). Results Results: We found that isoDGR and pTau immunoreactivities were similar across all assessed hippocampal regions including CA1, CA2/CA3 and entorhinal cortex (p=0.71), but isoDGR burden differed across disorder groups in all regions (CA1: p=0.008; CA2/3: p<0.001; entorhinal cortex: p=0.05). VaD had higher isoDGR concentrations in all hippocampal regions and was the only group with strong positive correlations between isoDGR and pTau levels (r=.86, p<0.01). AD subjects showed significantly higher levels of pTau and co-localisations in all regions. However, isoDGR exceeded pTau quantity in all hippocampal regions. Conclusions Conclusions: We noted isoDGR to be significantly high in VaD in the general absence of pTau or neurofibrillary pathology. While isoDGR may be used as a potential biomarker for this subtype of dementia, greater concentrations of isoDGR compared to pTau suggests it may precede and promote neurofibrillary pathology. This also highlights anti-isoDGR as a potential therapeutic target in dementia.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 teacher head, 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".