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Record W3109359388 · doi:10.1126/sciadv.abd1327

Patient-centered connectivity-based prediction of tau pathology spread in Alzheimer’s disease

2020· article· en· W3109359388 on OpenAlex
Nicolai Franzmeier, Anna Dewenter, Lukas Frontzkowski, Martin Dichgans, Anna Rubinski, Julia Neitzel, Ruben Smith, Olof Strandberg, Rik Ossenkoppele, Katharina Büerger, Marco Duering, Oskar Hansson, Michael Ewers

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueScience Advances · 2020
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsnot available
FundersNational Institute on AgingCanadian Institutes of Health ResearchParkinsonfondenNational Institutes of HealthIXICOH. Lundbeck A/SKnut och Alice Wallenbergs StiftelseServierSkånes universitetssjukhusVetenskapsrådetEisaiLunds UniversitetSvenska Forskningsrådet FormasNIH Clinical CenterF. Hoffmann-La RocheAustralian GovernmentBioClinicaBiogenPfizerNovartis Pharmaceuticals CorporationJanssen Alzheimer Immunotherapy Research And DevelopmentHjärnfondenBristol-Myers SquibbU.S. Department of DefenseEli Lilly and CompanyGenentechMarcus och Amalia Wallenbergs minnesfondAvid RadiopharmaceuticalsParkinson Research FoundationMeso Scale DiagnosticsAlzheimer's Association
KeywordsTau pathologyDiseasePathologyAlzheimer's diseaseMedicineNeuroscienceBiology

Abstract

fetched live from OpenAlex

In Alzheimer's disease (AD), the Braak staging scheme suggests a stereotypical tau spreading pattern that does, however, not capture interindividual variability in tau deposition. This complicates the prediction of tau spreading, which may become critical for defining individualized tau-PET readouts in clinical trials. Since tau is assumed to spread throughout connected regions, we used functional connectivity to improve tau spreading predictions over Braak staging methods. We included two samples with longitudinal tau-PET from controls and AD patients. Cross-sectionally, we found connectivity of tau epicenters (i.e., regions with earliest tau) to predict estimated tau spreading sequences. Longitudinally, we found tau accumulation rates to correlate with connectivity strength to patient-specific tau epicenters. A connectivity-based, patient-centered tau spreading model improved the assessment of tau accumulation rates compared to Braak stage-specific readouts and reduced sample sizes by ~40% in simulated tau-targeting interventions. Thus, connectivity-based tau spreading models may show utility in 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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.081
Threshold uncertainty score0.360

Codex and Gemma teacher scores by category

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

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.

Opus teacher head0.044
GPT teacher head0.331
Teacher spread0.287 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it