A Comprehensive Characterization of the Phospholipid and Cholesterol Composition of the Uncinate Fasciculus in the Human Brain: Evidence of Age‐Related Alterations
Bibliographic record
Abstract
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
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".