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Record W2948296075 · doi:10.1038/s41467-019-10217-w

Aβ-induced vulnerability propagates via the brain’s default mode network

2019· article· en· W2948296075 on OpenAlexafffund
Tharick A. Pascoal, Sulantha Mathotaarachchi, Min Su Kang, Sara Mohaddes, Monica Shin, Ah Yeon Park, Maxime Parent, Andréa Lessa Benedet, Mira Chamoun, Joseph Therriault, Heungsun Hwang, A. Claudio Cuello, Bratislav Misic, Jean‐Paul Soucy, John A. D. Aston, Serge Gauthier, Pedro Rosa‐Neto

Bibliographic record

VenueNature Communications · 2019
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsMcGill University Health CentreMcGill UniversityMontreal Neurological Institute and Hospital
FundersEngineering and Physical Sciences Research CouncilNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchNational Institute on AgingAlzheimer Society Research ProgramUniversity of California, San DiegoGenentechNational Institutes of HealthIXICOH. Lundbeck A/SServierEisaiGovernment of CanadaWeston Brain InstituteNorthern California Institute for Research and EducationPfizerBiogenBioClinicaF. Hoffmann-La RocheUniversity of Southern CaliforniaEli Lilly and CompanyU.S. Department of DefenseMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeNovartis Pharmaceuticals CorporationAlzheimer SocietyBristol-Myers SquibbConsortium canadien en neurodégénérescence associée au vieillissementAlzheimer's AssociationFoundation for the National Institutes of Health
KeywordsDefault mode networkDementiaPositron emission tomographyCognitive declineNeuroscienceVulnerability (computing)Mechanism (biology)CognitionGenetically modified mouseDiseaseAmyloid (mycology)PsychologyMedicineBiologyTransgeneInternal medicineComputer sciencePathologyPhysicsBiochemistry

Abstract

fetched live from OpenAlex

Abstract The link between brain amyloid-β (Aβ), metabolism, and dementia symptoms remains a pressing question in Alzheimer’s disease. Here, using positron emission tomography ([ 18 F]florbetapir tracer for Aβ and [ 18 F]FDG tracer for glucose metabolism) with a novel analytical framework, we found that Aβ aggregation within the brain’s default mode network leads to regional hypometabolism in distant but functionally connected brain regions. Moreover, we found that an interaction between this hypometabolism with overlapping Aβ aggregation is associated with subsequent cognitive decline. These results were also observed in transgenic Aβ rats that do not form neurofibrillary tangles, which support these findings as an independent mechanism of cognitive deterioration. These results suggest a model in which distant Aβ induces regional metabolic vulnerability, whereas the interaction between local Aβ with a vulnerable environment drives the clinical progression of dementia.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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 communication0.0000.001
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.035
GPT teacher head0.373
Teacher spread0.337 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations91
Published2019
Admission routes2
Has abstractyes

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