Defining the role of the Alzheimer disease risk factor CD2AP in brain vascular function
Bibliographic record
Abstract
Abstract Background Brain hypoperfusion is the earliest change observed in Alzheimer’s Disease (AD) brains. Degeneration of the brain vasculature, that includes cerebral amyloid pathology, white matter hyperintensities and cortical infracts, isomnipresent in AD, and predicts the progression of cognitive decline in AD patients. CD2‐associated protein (CD2AP) functions as scaffolding protein for cytoskeletal remodeling, membrane trafficking during clathrin‐mediated receptor endocytosis and cell‐cell interactions. Interestingly, polymorphisms in CD2AP constitute one of the top 10 genetic predisposition factor to AD. Since CD2AP is enriched in brain endothelial cells (BECs) that form the brain microvessels, we reason that the protein plays a key role in BECs and therefore, defects in CD2AP may contribute to cerebrovascular dysfunction observed in AD. Method We use a multidisciplinary approach (culture of primary BECs and cerebral arteries, two‐photon brain imaging of awake active mice and analysis of isolated brain microvessels from human AD volunteers) to investigate the role of CD2AP in BECs and brain vascular function. Result We found that 1) CD2AP regulates the Apolipoprotein E receptor 2 (ApoER2) in BECs, 2) the CD2AP/ApoER2 axis is key for brain vascular function in vitro and in vivo and 3) human AD volunteers have altered the levels of CD2AP and this alteration is associated with cognitive dysfunction. Conclusion We propose that the deregulation of the ApoER2/CD2AP axis contributes to the vascular defects observed in AD.
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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) | 0.001 | 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".