14‐3‐3σ up‐regulation in the temporal cortex associates with tau pathology and reactive astroglia in Lewy body disorders
Bibliographic record
Abstract
The 14-3-3 protein family plays a crucial role in cellular signaling and neuronal survival. Although 14-3-3 isoforms have been involved in the etiology of some neurodegenerative disorders, their role remains poorly understood in alpha-synucleinopathies. In this study, we wanted to characterize 14-3-3 gene expression patterns in the brain and periphery of patients with Lewy body pathology (LBP). We analyzed messenger RNA (mRNA) expression of all seven 14-3-3 isotypes in the temporal cortex and caudate nucleus of brains with pure and common LBP, as well as in cerebrospinal fluid, peripheral blood, and platelets. Stratifin (SFN) protein expression was assessed by immunohistochemistry and enzyme-linked immunosorbent assay. Effects of SFN overexpression on astrocyte activation were investigated in vitro. In the temporal cortex of LBP patients, six out of seven 14-3-3 genes were significantly downregulated, while SFN was markedly up-regulated. SFN protein localized to neurofibrillary tangles in the parahippocampal region and reactive astrocytes in white matter. In vitro, SFN treatment induced biphasic changes in astrocytic glial fibrillary acidic protein expression, suggesting a role in glial activation. Peripheral analysis revealed no significant 14-3-3 mRNA changes in blood, but platelet expression patterns inversely correlated with brain tissue; six isoforms were up-regulated, and SFN was strongly downregulated in dementia with Lewy bodies (DLB) platelets. Our findings revealed an important shift in 14-3-3 isotype expression in the temporal cortex of LBP patients, where SFN up-regulation reflected its colocalization with tau pathology and astrocytic reactivity. The inverse expression profile in platelets in DLB highlights their potential as accessible biomarkers for molecular changes occurring in the brain.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".