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Record W4387460339 · doi:10.1101/2023.10.05.560956

ABI3 deletion in TgCRND8 mice is associated with reduced amyloid plaque pathology and altered glial response

2023· preprint· en· W4387460339 on OpenAlexafffund
Deniz Ghaffari, Jennifer K. Griffin, Peter St George‐Hyslop

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
Topic14-3-3 protein interactions
Canadian institutionsOccupational Cancer Research CentreUniversity of Toronto
FundersCanadian Institutes of Health ResearchAlzheimer SocietyConsortium canadien en neurodégénérescence associée au vieillissement
KeywordsMicrogliaGenetically modified mouseGene knockinBiologyAlzheimer's diseaseAmyloid (mycology)TransgenePathologyLoss functionAmyloid precursor proteinNeuroscienceGeneticsImmunologyGenePhenotypeMedicineDiseaseInflammation

Abstract

fetched live from OpenAlex

Abstract Recent genome-wide association studies (GWAS) have identified several rare coding variants in a cluster of immune-related genes that are significantly associated with Alzheimer’s disease. This includes the risk variant (S209F) in ABI3 , a gene encoding the Abl Interactor family member 3 protein that is highly expressed in microglia, but little is known about its function in these cells and its association with AD. We have investigated the effects of ABI3 deletion on AD pathological features in the transgenic (Tg) CRND8 APP mouse model by immunofluorescence (IF) staining and confocal microscopy. We have observed that ABI3 expression is localized to microglia in the mouse brain and that the ABI3 immunoreactivity levels are increased in the TgCRND8 mice. The loss of ABI3 leads to a significant reduction of amyloid plaque numbers and size in the 9-month-old TgCRND8 mice. This is also accompanied by a reduced number of microglia clustering around the plaques. On the basis of these observations, we hypothesize that the loss of ABI3 may lead to changes in microglial behavior which directly or indirectly leads to reduced AD pathology in mice.

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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
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 score0.128
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
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 head0.014
GPT teacher head0.237
Teacher spread0.223 · 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 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

Citations3
Published2023
Admission routes2
Has abstractyes

Explore more

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