Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Full frame distilled prediction
Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
- Candidate categories
- none
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: ObservationalConsensus signal: Observational
- Genre
- Candidate signal: EmpiricalConsensus signal: Empirical
- Teacher disagreement score
- 0.131
- Threshold uncertainty score
- 0.881
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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.
- Teacher spread
- 0.363 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
Abstract An unresolved question for the understanding of Alzheimer’s disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts ( n = 1,016), we tested whether astrocyte reactivity modulates the association of Aβ with tau phosphorylation in CU individuals. We found that Aβ was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast + ). Cross-sectional and longitudinal tau–positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of Aβ only in CU Ast + individuals. Our findings suggest astrocyte reactivity as an important upstream event linking Aβ with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
The record
- Venue
- Nature Medicine
- Topic
- Alzheimer's disease research and treatments
- Field
- Medicine
- Canadian institutions
- Centre Intégré Universitaire de Santé et de Services Sociaux du Centre-Sud-de-l'Île-de-MontréalMontreal Neurological Institute and HospitalCentre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-JeanMcGill UniversityDouglas Mental Health University Institute
- Funders
- Fonds de Recherche du Québec - SantéHORIZON EUROPE Framework ProgrammeNational Institutes of HealthOlav Thon StiftelsenNational Heart, Lung, and Blood InstituteUK Dementia Research InstituteVetenskapsrådetHjärnfondenConselho Nacional de Desenvolvimento Científico e TecnológicoCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorEU Joint Programme – Neurodegenerative Disease ResearchEuropean CommissionStiftelsen för Gamla TjänarinnorFamiljen Erling-Perssons StiftelseBrightFocus FoundationNational Institute on AgingAlzheimer's AssociationConsortium canadien en neurodégénérescence associée au vieillissementCanadian Institutes of Health ResearchAlzheimerfondenWeston Brain InstituteAlzheimer's Drug Discovery Foundation
- Keywords
- AstrocytePathologicalPathophysiologyAlzheimer's diseaseBiomarkerTau pathologyPhosphorylationNeurosciencePathologyDiseasePsychologyMedicineChemistryCentral nervous systemBiochemistry
- Has abstract in OpenAlex
- yes