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Record W4293104004 · doi:10.1126/scitranslmed.abc8693

Intrinsic connectivity of the human brain provides scaffold for tau aggregation in clinical variants of Alzheimer’s disease

2022· article· en· W4293104004 on OpenAlexafffund
Joseph Therriault, Tharick A. Pascoal, Mélissa Savard, Sulantha Mathotaarachchi, Andréa Lessa Benedet, Mira Chamoun, Cécile Tissot, Firoza Z Lussier, Nesrine Rahmouni, Jenna Stevenson, Muhammad Naveed Iqbal Qureshi, Min Su Kang, Émilie Thomas, Paolo Vitali, Jean‐Paul Soucy, Gassan Massarweh, Paramita Saha‐Chaudhuri, Serge Gauthier, Pedro Rosa‐Neto

Bibliographic record

VenueScience Translational Medicine · 2022
Typearticle
Languageen
FieldNeuroscience
TopicFunctional Brain Connectivity Studies
Canadian institutionsMcGill UniversityCentre Intégré Universitaire de Santé et de Services Sociaux du Centre-Sud-de-l'Île-de-MontréalMontreal Neurological Institute and Hospital
FundersCanadian Institutes of Health Research
KeywordsNeuroscienceNeurodegenerationPhenotypeHuman brainBiologyDiseaseVulnerability (computing)Alzheimer's diseasePsychologyMedicineComputer scienceGeneticsPathologyGene

Abstract

fetched live from OpenAlex

Alzheimer's disease (AD) phenotypes might result from differences in selective vulnerability. Evidence from preclinical models suggests that tau pathology has cell-to-cell propagation properties. Therefore, here, we tested the cell-to-cell propagation framework in the amnestic, visuospatial, language, and behavioral/dysexecutive phenotypes of AD. We report that each AD phenotype is associated with a distinct network-specific pattern of tau aggregation, where tau aggregation is concentrated in brain network hubs. In all AD phenotypes, regional tau load could be predicted by connectivity patterns of the human brain. Furthermore, regions with greater connectivity displayed similar rates of longitudinal tau accumulation in an independent cohort. Connectivity-based tau deposition was not restricted to a specific vulnerable network but was rather a general property of brain organization, linking selective vulnerability and transneuronal spreading models of neurodegeneration. Together, this study indicates that intrinsic brain connectivity provides a framework for tau aggregation across diverse phenotypic manifestations of AD.

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.

How this classification was reachedexpand

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)0.004
metaresearch head score (Gemma)0.021
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.679
Threshold uncertainty score0.987

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0040.021
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.002
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 head0.106
GPT teacher head0.368
Teacher spread0.262 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations49
Published2022
Admission routes2
Has abstractyes

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