Alzheimer-related pathogenesis is dependent on neuronal receptor PTPσ
Bibliographic record
Abstract
Abstract Due to limited understanding of disease mechanisms and the lack of molecular targets, translational research for Alzheimer disease has not been fruitful hitherto. Here we report findings that indicate neuronal receptor phosphatase PTPσ as a potential therapeutic target for this dementia. In two TgAPP mouse models, a spectrum of Alzheimer-related pathologies, including aged-induced progression of β-amyloidosis, Tau aggregation, neuroinflammation, synaptic loss, as well as behavioral deficits, all show unambiguous dependency on PTPσ. APP amyloidogenic metabolites diminish upon PTPσ genetic depletion or pharmacological inhibition. Binding to APP in the brain, PTPσ regulates APP proteolytic metabolism via its phosphatase activity, likely through downstream signaling that modulates APP membrane localization and affinity to the β-secretase, in a specific manner that does not broadly affect β- and γ-secretase processing of other major substrates. Together, these findings unveil a gatekeeping role of PTPσ upstream in Alzheimer-like pathogenic pathway.
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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) | 0.001 | 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".