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Biomarker modeling of Alzheimer’s disease using PET-based Braak staging

2022· article· en· 304 citations· W4224620999 on OpenAlex· 10.1038/s43587-022-00204-0

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.

Canadian affiliationAn author listed a Canadian institution. This is the only route the usual frame has.
Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

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: Simulation or modelingConsensus signal: none
Genre
Candidate signal: EmpiricalConsensus signal: Empirical
Teacher disagreement score
0.811
Threshold uncertainty score
0.767
Validation status
machine_predicted_unvalidated · codex-gemma-dda1882f352a

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.051
GPT teacher head0.359
Teacher spread
0.308 · 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 Gold-standard diagnosis of Alzheimer’s disease (AD) relies on histopathological staging systems. Using the topographical information from [ 18 F]MK6240 tau positron-emission tomography (PET), we applied the Braak tau staging system to 324 living individuals. We used PET-based Braak stage to model the trajectories of amyloid-β, phosphorylated tau (pTau) in cerebrospinal fluid (pTau 181 , pTau 217 , pTau 231 and pTau 235 ) and plasma (pTau 181 and pTau 231 ), neurodegeneration and cognitive symptoms. We identified nonlinear AD biomarker trajectories corresponding to the spatial extent of tau-PET, with modest biomarker changes detectable by Braak stage II and significant changes occurring at stages III–IV, followed by plateaus. Early Braak stages were associated with isolated memory impairment, whereas Braak stages V–VI were incompatible with normal cognition. In 159 individuals with follow-up tau-PET, progression beyond stage III took place uniquely in the presence of amyloid-β positivity. Our findings support PET-based Braak staging as a framework to model the natural history of AD and monitor AD severity in living humans.

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 Aging
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-MontréalCentre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-JeanMcGill UniversityDouglas Mental Health University Institute
Funders
Fonds de Recherche du Québec - SantéNational Institutes of HealthOlav Thon StiftelsenUK Dementia Research InstituteVetenskapsrådetHjärnfondenEuropean CommissionGovernment of CanadaAlzheimer's SocietyEU Joint Programme – Neurodegenerative Disease ResearchNational Institute on AgingAlzheimer's AssociationConsortium canadien en neurodégénérescence associée au vieillissementCanadian Institutes of Health ResearchWeston Brain InstituteStiftelsen för Gamla TjänarinnorFamiljen Erling-Perssons StiftelseFaculty of Medicine, McGill UniversityFondation Brain CanadaMcGill University
Keywords
BiomarkerNeurodegenerationPositron emission tomographyStage (stratigraphy)PathologyDiseaseCognitive impairmentAlzheimer's diseaseNeuroimagingMedicinePsychologyAmyloid (mycology)Cognitive declineNeuroscienceDementiaBiology
Has abstract in OpenAlex
yes