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Record W2873769715 · doi:10.3389/fnins.2018.00476

Insulin-Like Growth Factor Binding Protein 2 Is Associated With Biomarkers of Alzheimer’s Disease Pathology and Shows Differential Expression in Transgenic Mice

2018· article· en· W2873769715 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

VenueFrontiers in Neuroscience · 2018
Typearticle
Languageen
FieldMedicine
TopicGDF15 and Related Biomarkers
Canadian institutionsnot available
FundersNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchUniversity of California, San DiegoNational Institutes of HealthIXICOH. Lundbeck A/SEisaiJanssen Alzheimer Immunotherapy Research And DevelopmentRainwater Charitable FoundationServierAmerican Society of NeuroradiologyNorthern California Institute for Research and EducationPfizerBiogenBioClinicaGenentechLarry L. Hillblom FoundationF. Hoffmann-La RocheJohnson and Johnson Pharmaceutical Research and DevelopmentRadiological Society of North AmericaUniversity of Southern CaliforniaNovartis Pharmaceuticals CorporationU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbAlzheimer's AssociationFoundation for the National Institutes of HealthAlzheimer's Disease Neuroimaging InitiativeMeso Scale Diagnostics
KeywordsGenetically modified mouseTransgeneInsulin-like growth factorDiseasePathologyGrowth factorBiologyMedicineNeuroscienceInternal medicineGeneBiochemistryReceptor

Abstract

fetched live from OpenAlex

There is increasing evidence that metabolic dysfunction plays an important role in Alzheimer’s disease (AD). Brain insulin resistance and subsequent impairment of insulin and insulin-like growth factor (IGF) signaling are thought to be linked with the neurodegenerative and clinical features of AD. Nevertheless, how the brain insulin/IGF signaling system is altered in AD and the effects of these changes on AD pathobiology are not well understood. IGF binding protein 2 (IGFBP-2) is an abundant cerebral IGF signaling protein and there is early evidence suggesting it associates with AD biomarkers. We evaluated the relationship between protein levels of IGFBP-2 with cerebrospinal fluid (CSF) biomarkers and neuroimaging markers of AD progression in 300 individuals from across the AD spectrum. CSF IGFBP-2 levels were correlated with CSF tau levels and brain atrophy in non-hippocampal regions. To further explore the role of IGFBP2 in tau pathobiology, we evaluated the expression of IGFBP2 brain tissue from transgenic mouse models of tauopathy (P301L-tau) as well as AD (TASTPM) and determined the cell types that most highly express IGFBP2. IGFBP2 expression in transgenic mouse models of neurodegenerative disease was only significantly different from wild-type mice in cortex, but not in hippocampus. In both humans and mice, IGFBP2 is most highly expressed in astrocytes. Taken together, our findings suggest that IGFBP-2 may be linked to tau pathology and provides further evidence for a relationship between metabolic dysregulation and neurodegeneration. Our results also raise the possibility that this relationship may extend beyond neurons.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.606
Threshold uncertainty score0.568

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
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 head0.017
GPT teacher head0.245
Teacher spread0.227 · 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