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Record W4388728643 · doi:10.1038/s41593-023-01484-4

Cryo-EM of Aβ fibrils from mouse models find tg-APPArcSwe fibrils resemble those found in patients with sporadic Alzheimer’s disease

2023· article· en· W4388728643 on OpenAlexaff
Mara Zielinski, Fernanda S. Peralta Reyes, Lothar Gremer, Sarah Schemmert, Benedikt Frieg, Luisa U. Schäfer, Antje Willuweit, L Donner, Margitta Elvers, Lars Nilsson, Stina Syvänen, Dag Sehlin, Martin Ingelsson, Dieter Willbold, Gunnar F. Schröder

Bibliographic record

VenueNature Neuroscience · 2023
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsOntario Brain InstituteUniversity of TorontoUniversity Health Network
FundersLandesamt für Natur, Umwelt und Verbraucherschutz Nordrhein-WestfalenAlzheimerfondenBundesministerium für Bildung und ForschungHjärnfondenForschungszentrum JülichVetenskapsrådetHelmholtz AssociationAlzheimer Forschung Initiative
KeywordsFibrilGenetically modified mouseAmyloid (mycology)PathologyAlzheimer's diseaseEx vivoProtein filamentAmyloid fibrilDiseaseTransgeneNeuroscienceChemistryAmyloid βBiophysicsMedicineBiologyIn vitroBiochemistryGene

Abstract

fetched live from OpenAlex

Abstract The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer’s disease. However, the properties of Aβ in such mice have not been systematically compared to Aβ in the brains of patients with Alzheimer’s disease. Here, we determined the structures of nine ex vivo Aβ fibrils from six different mouse models by cryogenic-electron microscopy. We found novel Aβ fibril structures in the APP/PS1, ARTE10 and tg-SwDI models, whereas the human type II filament fold was found in the ARTE10, tg-APP Swe and APP23 models. The tg-APP ArcSwe mice showed an Aβ fibril whose structure resembles the human type I filament found in patients with sporadic Alzheimer’s disease. A detailed assessment of the Aβ fibril structure is key to the selection of adequate mouse models for the preclinical development of novel plaque-targeting therapeutics and positron emission tomography imaging tracers in Alzheimer’s disease.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.017
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0000.001
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 head0.045
GPT teacher head0.325
Teacher spread0.281 · 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

Citations50
Published2023
Admission routes1
Has abstractyes

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