Controversies over p25 in Alzheimer's disease
Bibliographic record
Abstract
Activity of the neuronal Cdc2-like kinase composed of cyclin-dependent kinase 5 (Cdk5) and its activator, p35, is critical for the normal development of the central nervous system, including cortical lamination and axonal patterning events. Conversely, altered Cdk5 activity has been associated with several neuronal defects including neurodegeneration. Indeed, an increasing line of evidence suggests that Cdk5 contributes to neurodegeneration in AD. For example, Cdk5 immunoreactivity is consistently detected in neurofibrillary tangles (NFTs) [15]; Cdk5 phosphorylates tau and promotes dimerization of tau to an AD-like state [2, 13]; sulfated glycosaminoglycans co-exist with tau and Cdk5 in NFTs and remarkably enhance tau phosphorylation by Cdk5 [5]; protein phosphatase 1 (PP1), which shows decreased activity in AD brains [4], is inhibited by Cdk5 through phosphorylation of the PP1 inhibitor protein (I-1) [6]; in primary neuronal cultures, Aβ induces activation of Cdk5 that results in tau hyperphosphorylation, cytoskeletal collapse, and cell death [1, 9]. In addition, we and others have shown elevated Cdk5 activity in mice exhibiting tau hyperphosphorylation [10], and in AD brains [7,11]. However, the molecular mechanisms whereby Cdk5 activity is upregulated in AD brain remain to be investigated. Recently, it was suggested that Cdk5 activity is enhanced by calcium through induction of p35 cleavage to p25 via calpain activation [9]. The active truncated form of p35, p25, was then shown to accumulate in
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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 | 0.008 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.005 |
| Scholarly communication | 0.002 | 0.005 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.006 | 0.008 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".