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Record W4307833411 · doi:10.1101/2022.10.30.514365

Whole-brain modeling of the differential influences of Amyloid-Beta and Tau in Alzheimer’s Disease

2022· preprint· en· W4307833411 on OpenAlexfundno aff
Gustavo Patow, Leon Stefanovski, Petra Ritter, Gustavo Deco, Xenia Kobeleva

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldNeuroscience
TopicFunctional Brain Connectivity Studies
Canadian institutionsnot available
FundersHORIZON EUROPE European Innovation CouncilH2020 European Research CouncilNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICOH. Lundbeck A/SServierEisaiMinisterio de Ciencia e InnovaciónNorthern California Institute for Research and EducationJoachim Herz StiftungPfizerBiogenBioClinicaF. Hoffmann-La RocheUniversity of Southern CaliforniaH2020 Research InfrastructuresEli Lilly and CompanyU.S. Department of DefenseMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeNovartis Pharmaceuticals CorporationBristol-Myers SquibbAlzheimer's AssociationHorizon 2020 Framework ProgrammeFoundation for the National Institutes of Health
KeywordsNeuroscienceDiseaseTau proteinIn silicoBETA (programming language)Amyloid betaAlzheimer's diseaseAmyloid (mycology)BiologyPsychologyMedicineComputer sciencePathologyGenetics

Abstract

fetched live from OpenAlex

Abstract Background Alzheimer’s Disease is a neurodegenerative condition associated with the accumulation of two misfolded proteins, amyloid-beta (A β ) and tau. We study their effect on neuronal activity, with the aim of assessing their individual and combined impact. Methods We use a whole-brain dynamic model to find the optimal parameters that best describe the effects of A β and tau on the excitation-inhibition balance of the local nodes. Results We found a clear dominance of A β over tau in the early disease stages (MCI), while tau dominates over A β in the latest stages (AD). We identify crucial roles for A β and tau in complex neuronal dynamics and demonstrate the viability of using regional distributions to define models of large-scale brain function in AD. Conclusions Our study provides further insight into the dynamics and complex interplay between these two proteins, opening the path for further investigations on biomarkers and candidate therapeutic targets in-silico.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.013
Threshold uncertainty score0.026

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.000
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 head0.038
GPT teacher head0.249
Teacher spread0.211 · 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 designSimulation or modeling
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

Citations2
Published2022
Admission routes1
Has abstractyes

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