O3‐10‐06: BRAIN EPIGENETIC CHANGES MEASURED WITH THE NOVEL [<sup>11</sup>C]MARTINOSTAT PET MEDIATE THE EFFECTS OF AMYLOID AND TAU PET DEPOSITION ON COGNITION
Bibliographic record
Abstract
Epigenetics occur via the interaction of genome with environment. Although epigenetic modifications have been clarified in other diseases such as cancer, its involvement in AD is unknown. Among different types of modifications, histone acetylation is the most frequently associated with memory. Acetylation of histones diminishes the affinity between adjacent histones and configures an open-chromatin structure, allowing increasing in genes’ expression. [C]Martinostat is a novel PET agent that selectively binds to histone deacetylase class I, which induces changes in genes such as BDNF, SYP, and Progranulin. Here, we tested the hypothesis that epigenetic changes measured with [C]Martinostat mediate the effects of amyloid and tau in cognition. We studied 46 individuals across the AD spectrum (15 preclinical AD; 15 mild cognitive impairment; and 16 AD patients) with PET amyloid ([F]AZD4694), tau ([F]MK6240), and epigenetics ([C]Martinostat), as well as cognition (MMSE). Structured equation modeling (SEM) tested the hypothesis whether epigenetic modifications mediate the effects of amyloid and tau on cognition. The model was adjusted for age, gender, grey matter density, and diagnosis. Structural equation modelling (path analysis) We showed that reductions in histone deacetylase I strongly mediate the deleterious effects of amyloid and tau on cognition, and therefore may represent a disease-modifying therapeutic target for the AD, with promising clinical implications. It is important to mention that this is the first study measuring brain epigenetics in vivo in individuals with brain pathology.
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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 | 0.000 | 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) | 0.005 | 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".