Examination of mitochondrial function and synaptic proteins in male and female Alzheimer's disease postmortem brain
Bibliographic record
Abstract
BACKGROUND: Inflammation and mitochondrial impairments, driven by metabolic dysfunction, have been suggested to underly the synaptic damage seen with Alzheimer's disease. This study examined if human Alzheimer's disease brains have significant differences in metabolic, synaptic, and inflammatory markers compared to aged-matched control brains. Sex-specific differences were also examined as post-menopausal females disproportionally present with AD compared to age-matched males. METHODS: Prefrontal cortex samples were taken from post-mortem age-matched female and male donors with/without Alzheimer's disease (n = 10 per sex and condition). Samples were prepared and analysed by immunofluorescence, western blot, ELISA-based inflammatory cytokine panels, and mitochondrial respiration analysis. RESULTS: Both AD males and females had higher Akt phosphorylation (p = 0.0064) but only AD males had higher downstream mTOR phosphorylation (p = 0.0363). AD samples had greater mitochondrial complex III (p = 0.0186), and V (p = 0.0341) content compared to controls while control males had less complex IV than control females (p = 0.0105). No difference in complex I respiration was found for any group, but AD females had lower Complex IV respiration compared to female controls (p = 0.0013). AD individuals had greater expression of synaptic markers AMPA GluA1 (p = 0.0256) and synaptophysin (p = 0.0432). Only AD females had a higher expression in the synaptic marker ELKS1 in white matter (p = 0.0116). Only the cytokine IL-2 was found to be greater in AD individuals (p = 0.0390). Total Iba-1 content was different between groups in both gray and white matter where Iba-1 was lower in both AD females and males in gray matter (p = 0.0296), and AD females had higher Iba-1 compared to all other groups in white matter (p = 0.0245). Microglia were then assigned as having either ameboid, hypertrophic, dystrophic, ramified, or rod-like morphology. Rod-like microglia were lower in the grey matter of AD samples (p = 0.0345) and there were no differences by sex. CONCLUSION: We demonstrate differences in Akt signaling and mitochondrial content in PFC samples from AD donors. Additionally, this study shows greater changes in metabolic signaling in females than in males, and that this dysregulation in signaling with AD development is unique to females when compared to males.
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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) | 0.002 | 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".