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Record W4392885252 · doi:10.1002/bdd.2386

Aging and brain free cholesterol concentration on amyloid‐β peptide accumulation in guinea pigs

2024· article· en· W4392885252 on OpenAlex
K. Sandy Pang, Hao Peng, Betty P. Li, Binyu Wen, Keumhan Noh, Runyu Xia, Anja Toscan, Sylvia Serson, Paul E. Fraser, Rommel G. Tirona, Inés A.M. de Lannoy

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.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueBiopharmaceutics & Drug Disposition · 2024
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsWestern UniversityOccupational Cancer Research CentreUniversity of Toronto
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsPeptideCholesterolAmyloid (mycology)Guinea pigEndocrinologyInternal medicineβ amyloidChemistryPharmacologyAlzheimer's diseaseMedicineBiochemistryPathology

Abstract

fetched live from OpenAlex

Abstract Alzheimer’s disease is a complex multifactorial neurodegenerative disorder wherein age is a major risk factor. The appropriateness of the Hartley guinea pig (GP), which displays high sequence homologies of its amyloid‐β (Aβ 40 and Aβ 42 ) peptides, Mdr1 and APP (amyloid precursor protein) and similarity in lipid handling to humans, was appraised among 9–40 weeks old guinea pigs. Protein expression levels of P‐gp ( Abcb1 ) and Cyp46a1 (24(S)‐hydroxylase) for Aβ 40 , and Aβ 42 efflux and cholesterol metabolism, respectively, were decreased with age, whereas those for Lrp1 (low‐density lipoprotein receptor related protein 1), Rage (receptor for advanced glycation endproducts) for Aβ efflux and influx, respectively, and Abca1 (the ATP binding cassette subfamily A member 1) for cholesterol efflux, were unchanged among the ages examined. There was a strong, negative correlation of the brain Aβ peptide concentrations and Abca1 protein expression levels with free cholesterol. The correlation of Aβ peptide concentrations with Cyp46a1 was, however, not significant, and concentrations of the 24(S)‐hydroxycholesterol metabolite revealed a decreasing trend from 20 weeks old toward 40 weeks old guinea pigs. The composite data suggest a role for free cholesterol on brain Aβ accumulation. The decreases in P‐gp and Lrp1 protein levels should further exacerbate the accumulation of Aβ peptides in guinea pig brain.

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 score0.296
Threshold uncertainty score0.657

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 head0.045
GPT teacher head0.382
Teacher spread0.338 · 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