Sirtuin 1 Reduction Parallels the Accumulation of Tau in Alzheimer Disease
Bibliographic record
Abstract
Aging and metabolism-related disorders are risk factors for Alzheimer disease (AD). Because sirtuins may increase the life span through regulation of cellular metabolism, we compared the concentration of sirtuin 1 (SIRT1) in the brains of AD patients (n = 19) and controls (n = 22) using Western immunoblots and in situ hybridization. We report a significant reduction of SIRT1 (messenger RNA [mRNA], -29%; protein, -45%) in the parietal cortex of AD patients, but not in the cerebellum. Further analyses in a second cohort of 36 subjects confirmed that cortical SIRT1 was decreased in AD but not in individuals with mild cognitive impairment. SIRT1 mRNA and its translated protein correlated negatively with the duration of symptoms (mRNA, r2 = -0.367; protein, r2 = -0.326) and the accumulation of paired helical filament tau (mRNA, r2 = -0.230; protein, r2 = -0.119), but weakly with insoluble amyloid-beta 42 (mRNA, r2= -0.090; protein, r2 = -0.072). A significant relationship between SIRT1 levels and global cognition scores proximate to death was also found (r2= +0.09, p = 0.049). In contrast, cortical SIRT1 levels remained unchanged in a triple-transgenic animal model of AD. Collectively, our results indicate that loss of SIRT1 is closely associated with the accumulation of amyloid-beta and tau in the cerebral cortex of persons with AD.
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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".