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Record W4415116021 · doi:10.1101/2025.10.12.681536

A Comprehensive Characterization of the Phospholipid and Cholesterol Composition of the Uncinate Fasciculus in the Human Brain: Evidence of Age‐Related Alterations

2025· preprint· en· W4415116021 on OpenAlexafffund
Kelly Perlman, Chuck T. Chen, Mackenzie E. Smith, John J. Kim, Gustavo Turecki, Richard P. Bazinet, Naguib Mechawar

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldMedicine
TopicAdvanced Neuroimaging Techniques and Applications
Canadian institutionsUniversity of TorontoMcGill University
FundersFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchCanada First Research Excellence FundNatural Sciences and Engineering Research Council of CanadaFondation Brain Canada
KeywordsUncinate fasciculusMyelinPhospholipidWhite matterCholesterolCortex (anatomy)Depression (economics)TriglyceridePrefrontal cortex

Abstract

fetched live from OpenAlex

ABSTRACT The uncinate fasciculus (UF) is a long‐range association fiber tract connecting the anterior temporal lobe with the orbitofrontal cortex and has been linked to a multitude of physiological and pathophysiological conditions such as aging, epilepsy, and the vulnerability to psychopathology posed by a history of childhood abuse (CA). Since the myelin sheath is highly enriched in lipids, changes in white matter (WM) microstructure observed via neuroimaging may reflect alterations in the myelin lipid profile. Given that the UF does not exist in rodents, its molecular properties are highly understudied. Therefore, we sought to quantify the phospholipid FA and cholesterol quantities of the human postmortem UF and evaluate any lipid‐related or myelin‐constituent gene/protein changes associated with age and history of CA. UF samples were analyzed from individuals with depression who died by suicide with (DS‐CA) or without (DS) severe CA, and control individuals (CTRL), with an age span of 15 to 85 years. Phospholipids were separated by thin‐layer chromatography; FAs and nonderivatized cholesterol were quantified by gas chromatography‐flame ionization detection. The relative expression of myelin‐constituent genes and proteins was measured by RT‐qPCR and immunoblotting, respectively. We found no robust relationships between CA or depression and lipid measures or myelin‐constituent gene/protein levels. In contrast, phospholipids showed pronounced age effects that differed by fraction, with an overall trend of monounsaturated FAs increasing and long‐chain omega‐6 polyunsaturated FAs decreasing with age. The expression of most myelin‐constituent genes and proteins declined with age; PLP1 and MAG showed significant decreases. Therefore, changes in lipid composition and lipid‐protein interactions likely contribute to age‐related myelin deficits and may in part underlie age‐associated cognitive decline. image

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)0.000
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.040
GPT teacher head0.302
Teacher spread0.262 · 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 routes2
Has abstractyes

Explore more

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