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Record W2763217028 · doi:10.1111/bpa.12567

Downregulated apoptosis and autophagy after anti‐Aβ immunotherapy in Alzheimer's disease

2017· article· en· W2763217028 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueBrain Pathology · 2017
Typearticle
Languageen
FieldMedicine
TopicAutophagy in Disease and Therapy
Canadian institutionsnot available
FundersMedical Research CouncilFondation Philippe ChatrierFondation Philippe Wiener - Maurice AnspachUniversity of SouthamptonMedical Research Council CanadaUniversity Hospital Southampton NHS Foundation TrustJohns Hopkins University
KeywordsAutophagyApoptosisImmunotherapyDiseaseMedicineAlzheimer's diseaseCancer researchImmunologyBiologyPathologyImmune systemGenetics

Abstract

fetched live from OpenAlex

Abstract Aβ immunization of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) trial caused Aβ removal and a decreased density of neurons in the cerebral cortex. As preservation of neurons may be a critical determinant of outcome after Aβ immunization, we have assessed the impact of previous Aβ immunization on the expression of a range of apoptotic proteins in post‐mortem human brain tissue. Cortex from 13 AD patients immunized with AN1792 (iAD) and from 27 nonimmunized AD (cAD) cases was immunolabeled for proapoptotic proteins implicated in AD pathophysiology: phosphorylated c‐Jun N‐terminal kinase (pJNK), activated caspase3 (a‐casp3), phosphorylated GSK3β on tyrosine 216 (GSK3β tyr216 ), p53 and Cdk5/p35. Expression of these proteins was analyzed in relation to immunization status and other clinical data. The antigen load of all of these proapoptotic proteins was significantly lower in iAD than cAD ( P < 0.0001). In cAD, significant correlations ( P < 0.001) were observed between: Cdk5/p35 and GSK3β tyr216 ; a‐casp3 and Aβ 42 ; p53 and age at death. In iAD, significant correlations were found between GSK3β tyr216 and a‐casp3; both spongiosis and neuritic curvature ratio and Aβ 42 ; and Cdk5/p35 and Aβ‐antibody level. Although neuronal loss was increased by immunization with AN1792, our present findings suggest downregulation of apoptosis in residual neurons and other cells.

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.

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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.387
Threshold uncertainty score0.765

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
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 head0.014
GPT teacher head0.296
Teacher spread0.282 · 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