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Record W3036153982 · doi:10.1101/2020.06.02.20119578

Cerebrospinal fluid A beta 1-40 peptides increase in Alzheimer’s disease and are highly correlated with phospho-tau in control individuals

2020· preprint· en· W3036153982 on OpenAlexfundno aff
Sylvain Lehmann, Julien Dumurgier, Xavier Ayrignac, Cécilia Marelli, Daniel Alcolea, Juan Fortea, Éric Thouvenot, Constance Delaby, Christophe Hirtz, Jérôme Vialaret, Nelly Ginestet, Élodie Bouaziz-Amar, Jean Laplanche, Pierre Labauge, Claire Paquet, Alberto Lleó, Audrey Gabelle

Bibliographic record

VenuemedRxiv · 2020
Typepreprint
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsnot available
FundersNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICOH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationBioClinicaF. Hoffmann-La RocheUniversity of Southern CaliforniaBiogenU.S. Department of DefenseMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeNovartis Pharmaceuticals CorporationPfizerEli Lilly and CompanyBristol-Myers SquibbNational Institute on AgingAlzheimer's AssociationFoundation for the National Institutes of Health
KeywordsCerebrospinal fluidContext (archaeology)MedicineAlzheimer's diseasePathologyInternal medicineOdds ratioDiseaseGastroenterologyBiology

Abstract

fetched live from OpenAlex

ABSTRACT Background: Amyloid pathology, which is one of the characteristics of Alzheimer’s disease (AD), results from altered metabolism of the beta-amyloid peptide (Aβ) in terms of synthesis, clearance or aggregation. A decrease in cerebrospinal fluid (CSF) level Aβ 1-42 is evident in AD, and the CSF ratio Aβ 40 /Aβ 40 has recently been identified as one of the most reliable diagnostic biomarkers of amyloid pathology. Variations in inter-individual levels of Aβ 1-40 in the CSF have been observed in the past, but their origins remain unclear. In addition, the variation of Aβ 40 in the context of AD studied in several studies has yielded conflicting results. Methods Here, we analyzed the levels of Aβ 1-40 using multicenter data obtained on 2466 samples from six different cohorts in which CSF was collected under standardized protocols, centrifugation and storage conditions. Tau and p-tau(181) concentrations were measured using commercially available in vitro diagnostic immunoassays. Concentrations of CSF Aβ 1-42 and Aβ 1-40 were measured by ELISA, xMAP technology, chemiluminescence immunoassay (CLIA) and mass spectrometry. Statistical analyses were calculated for parametric and non-parametric comparisons, linear regression, correlation and odds ratios. The statistical tests were adjusted for the effects of covariates (age, in particular). Results: Regardless of the analysis method used and the cohorts, a slight but significant age-independent increase in the levels of Aβ 40 in CSF was observed in AD. We also found a strong positive correlation between the levels of Aβ 40 and p-tau(181) in CSF, particularly in control patients. Conclusions: These results indicate that an increase in the baseline level of amyloid peptides, which are associated with an increase in p-tau(181), may be a biological characteristic of AD. This confirms the potential therapeutic value of lowering the baseline levels of Aβ 40 which, being elevated, can be considered a risk factor for the 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 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)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
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 head0.029
GPT teacher head0.287
Teacher spread0.259 · 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 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

Citations1
Published2020
Admission routes1
Has abstractyes

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