Platelet-derived growth factor-BB and white matter hyperintensity burden in APOE4 carriers
Bibliographic record
Abstract
The apolipoprotein-e4 (APOE4) gene increases risk for developing late-onset Alzheimer's disease (AD) and has been linked to increased microvascular dysfunction, including pericyte degeneration and blood-brain barrier breakdown. Platelet-derived growth factor-BB (PDGF-BB) is a glycoprotein involved in blood-brain barrier and pericyte maintenance. Increased PDGF-BB levels have been reported in white matter in AD brain tissue. However, the association between circulating levels of PDGF-BB and cerebral white matter damage in older adults remains unknown. Participants included community-dwelling older adults (age range 55–90 years, M = 73.1 years; SD = 7.5; 61.0% male) from the Alzheimer's Disease Neuroimaging Initiative who underwent venipuncture and blood plasma immunoassay for PDGF-BB, brain MRI scanning with T2-FLAIR for volumetric quantification of white matter hyperintensities (WMH) and APOE4 genotyping (N = 64). Linear regression analyses examined the relationship between plasma PDGF-BB levels and WMH volume, adjusting for age, sex, intracranial volume (ICV) and stratifying by APOE4 status. Greater levels of circulating PDGF-BB were related to greater WMH volume, even after accounting for age, sex, ICV and APOE4 carrier status (p = 0.040). Nineteen (29.2%) were APOE4 carriers. When stratified by APOE4 status, the relationship between PDGF-BB and WMH volume was only significant for APOE4 carriers (p = 0.007), but not non-carriers (p = 0.448), after adjusting for age, sex and ICV. These findings reveal a differential relationship between PDGF-BB and WMH volume for APOE4 carriers versus non-carriers. The APOE4 variant leads to accelerated cerebrovascular injury and cognitive decline. Elevated levels of PDGF-BB in carriers may suggest a role for pericytes and blood-brain barrier dysfunction in white matter damage, vascular cognitive impairment and AD. Additional studies will elucidate the role of PDGF ligands and receptors in these conditions.
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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) | 0.002 | 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".