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Record W4205850289 · doi:10.1101/2022.01.12.22269196

Patients with Alzheimer’s disease have increased cellular amyloid uptake

2022· preprint· en· W4205850289 on OpenAlexfundno aff
Dmitry V. Zaretsky, Maria V. Zaretskaia, Yaroslav I. Molkov

Bibliographic record

VenuemedRxiv · 2022
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
KeywordsAlzheimer's Disease Neuroimaging InitiativeAmyloid (mycology)DiseaseCerebrospinal fluidAlzheimer's diseaseIntracellularβ amyloidInternal medicineMedicineEndocrinologyNeurosciencePsychologyPathologyBiologyBiochemistry

Abstract

fetched live from OpenAlex

ABSTRACT Amyloid plaques are the main signature of Alzheimer’s disease (AD). Beta-amyloid (Aβ) concentration in cerebrospinal fluid (CSF-Aβ) and the density of amyloid depositions have a strong negative correlation. However, AD patients have lower CSF-Aβ levels compared to cognitively normal people even after accounting for this correlation. The goal of this study was to infer variations of parameters in Aβ metabolism of AD patients that underlie this difference using data from the Alzheimer’s Disease Neuroimaging Initiative cohort. We found that AD patients had dramatically increased rates of cellular amyloid uptake compared to individuals with normal cognition (NC). A group with late-onset mild cognitive impairment (LMCI) also exhibited stronger amyloid uptake, however this was less pronounced than in the AD group. Estimated parameters in the early-onset MCI group did not differ significantly from those in the NC group. Aβ cytotoxicity depends on both the amount of peptide internalized by cells and its intracellular degradation into toxic products. Based on our results, we speculate that AD and LMCI are associated with increased cellular amyloid uptake which leads to faster disease progression, whereas the early-onset MCI may be mediated by the increased production of toxic amyloid metabolites.

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)0.000
metaresearch head score (Gemma)0.001
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 score0.004
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0040.001

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 head0.032
GPT teacher head0.289
Teacher spread0.258 · 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
Published2022
Admission routes1
Has abstractyes

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