[O3–11–04]: SERUM LONG‐CHAIN N‐3 FATTY ACID LEVELS ARE ASSOCIATED WITH PRESYNAPTIC PROTEINS IN THE HUMAN BRAIN
Bibliographic record
Abstract
Blood concentrations and intake of long chain n-3 polyunsaturated fatty acids (PUFAs) have been associated with cognitive decline and the development of dementia. Animal models suggest that one mechanism underlying this relation may be neuroprotection of n-3 PUFAs against loss in synaptic proteins. We report here the first human study to relate serum n-3 PUFA levels to brain tissue levels of presynaptic proteins. This study is based on 57 deceased participants of the Memory and Aging Project who underwent brain autopsy. Presynaptic protein concentrations in the brain and n-3 PUFA serum levels over a mean of 3.6 years with on average 2.7 biochemical assessments were determined. Brain concentrations of eight presynaptic proteins (complexin I and II, Sept5, SNAP-25, synaptophysin, synaptotagmin, syntaxin, and VAMP) were measured with monoclonal antibodies and ELISA techniques in 12 brain regions. Presynaptic protein levels for each region were log-transformed, standardized, and averaged across regions. Serum n-3 PUFA concentrations were averaged and determined in total ethanolamine plasmalogen (PL) and phosphatidylethanolamine (PE) by mass spectrometry. Linear regression models adjusting for age at death, sex and education level were used to assess the associations. In adjusted models PE docosahexaenoic acid (DHA) had linear associations with synaptophysin (β=1.18; SE=0.58, P=0.05), VAMP (β=1.03; SE=0.45, P=0.03), and SNAP-25 (β=1.20; SE=0.57, P=0.04) and marginal associations with syntaxin (β=1.09; SE=0.58, P=0.07) and Sept5 (β=0.85; SE=0.45, P=0.06). PL DHA showed significant associations with higher levels of complexin I and II (β=0.55; SE=0.22, P=0.02 and β=0.66; SE=0.28, P=0.02 respectively) and marginal associations with syntaxin (β=0.39; SE=0.22, P=0.09) and VAMP (β=0.34; SE=0.18, P=0.06). PL eicosapentaenoic acid (EPA) showed marginal linear associations with higher levels of synaptophysin (β=0.80; SE=0.43, P=0.07), synaptotagmin (β=0.68; SE=0.40, P=0.09), syntaxin (β=0.77; SE=0.43, P=0.08), VAMP (β=0.58; SE=0.34, P=0.10), SNAP-25 (β=0.73; SE=0.43, P=0.10), and Sept5 (β=0.63; SE=0.33, P=0.06). This study suggests that one potential biological mechanism underlying the relation of n-3 PUFAs, DHA in particular, to brain health during aging is maintenance of neural reserve by sustaining higher levels of presynaptic proteins.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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.
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".