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Record W4409276435 · doi:10.1101/2025.04.06.25325186

Association between epigenetic aging acceleration and amyloid biomarkers in bipolar disorder

2025· preprint· en· W4409276435 on OpenAlexaff
Gabriel R. Fries, Steven De La Garza, N. Zhao, A Bass, Camila N. C. Lima, Nobuhide Kobori, Tatiana Barichello, Gustavo Turecki, Paul E. Schulz, Breno S. Diniz, Jair C. Soares

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldMedicine
TopicBipolar Disorder and Treatment
Canadian institutionsMcGill UniversityDouglas Mental Health University Institute
Fundersnot available
KeywordsQuartileBrain agingBipolar disorderConfoundingInternal medicineMedicineEndocrinologyAlzheimer's diseasePsychologyDiseaseOncologyConfidence intervalLithium (medication)

Abstract

fetched live from OpenAlex

Abstract Objectives Bipolar disorder (BD) has been associated with an elevated risk of Alzheimer’s Disease (AD). We assessed AD biomarkers in BD and tested whether epigenetic aging (EA) acceleration is a potential mechanism driving variability in these markers. Design, Setting, Participants Cross-sectional study of n=59 living individuals with BD and n=20 age- and sex-equated control participants, as well as analyses of postmortem brain samples (Brodmann area 9/46) from n=46 individuals with BD. Measurements Amyloid beta (Aβ) 40 , Aβ 42 , and total Tau levels were measured in plasma from individuals with BD and controls, and Aβ 42 levels were measured in brains. EA and its acceleration (blood: GrimAge and DunedinPACE; brains: DNAmClock Cortical ) were estimated for all samples. Individuals with BD were split into quartiles with accelerated or slower EA if they were in the first or fourth quartiles for GrimAge acceleration (AgeAccelGrim), DunedinPACE, or DNAmClock Cortical acceleration (DNAmClock Cortical Accel). Results Individuals with BD showed an increase in Aβ 40 (p=.049) and a decrease in the Aβ 42/40 ratio (p=.035) compared to controls. A decrease in the Aβ 42/40 ratio was also found in individuals with BD with high versus low AgeAccelGrim (p=.028). Brain Aβ 42 levels significantly correlated with DNAmClock Cortical Accel (r 2 =.270, p=.007), with those with high EA acceleration showing higher brain Aβ 42 after controlling for confounders (p=.008). Conclusions Our results provide preliminary evidence that EA may explain the variability in AD risk in individuals with BD and could act as a target for preventing dementia and AD in BD.

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 score0.008

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 communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.019
GPT teacher head0.286
Teacher spread0.267 · 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

Citations0
Published2025
Admission routes1
Has abstractyes

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