Prion-like propagation and protein misfolding
Bibliographic record
Abstract
Prion protein (PrP) is best known for its association with prion diseases.However, a controversial new role for PrP in Alzheimer disease (AD) has recently emerged.In vitro studies and mouse models of AD suggest that PrP may be involved in AD pathogenesis through a highly specific interaction with amyloid-b (Ab42) oligomers.Immobilized recombinant human PrP (huPrP) also exhibited high affinity and specificity for Ab42 oligomers.Here we report for the first time that aggregated forms of huPrP and Ab42 are co-purified from brain extracts of AD brains.Moreover, an anti-PrP antibody and an agent that specifically binds to insoluble PrP (iPrP or silent prions) co-precipitate insoluble Ab from human AD brain.Finally, using a peptide membrane array of ninety-nine 13-mer peptides that span the entire sequence of mature huPrP, two types of Ab binding sites on huPrP are identified in vitro.One specifically binds to Ab42 and another indistinctively binds to both Ab42 and Ab40.Notably, Ab42-specific binding sites are mainly localized in the octapeptide repeat region, whereas indistinctive sites are mainly in the C-terminal domain of PrP.Our study suggests that iPrP is the major PrP species that interacts with insoluble Ab42 in vivo.While this work indicated the binding of Ab42 to huPrP in the AD brain, the pathophysiological relevance of iPrP/Ab42 interaction remains to be determined.
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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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".