The Alzheimer risk factor CD2AP causes dysfunction of the brain vascular network
Bibliographic record
Abstract
Abstract Genetic variations in CD2-associated protein (CD2AP) predispose to Alzheimer’s disease (AD) but the underlying mechanisms remain unknown. Here, we show that a cerebrovascular loss of CD2AP in AD is associated with cognitive decline and genetic downregulation of CD2AP in brain microvessels impairs memory function in two distinct mouse models. The memory deficits are linked to reduced cerebral blood flow during resting state and altered neurovascular coupling in pial vessels, arterioles and capillaries. In brain endothelial cells, CD2AP regulates the levels and signaling of ApoE receptor 2 (ApoER2). Activation of the CD2AP-ApoER2 pathway with Reelin glycoprotein mitigates the toxic effects of Aβ on capillary blood flow and on vasomotion of arterioles depleted of CD2AP. We propose that deregulation of CD2AP perturbs distinct segments of the brain vascular network, and harnessing the biology of specific brain vessel types may offer refined therapeutic strategies for the treatment of 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 | 0.000 | 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) | 0.004 | 0.001 |
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".