O1‐02‐01: A new pathogenic pathway and causative treatment option for Alzheimer's disease: From aging to mitochondrial and ABC transporter dysfunction
Bibliographic record
Abstract
In Alzheimer's disease (AD), the intracerebral accumulation of amyloid-b (Ab) peptides is a critical yet poorly understood process. Ab clearance via the blood-brain barrier is reduced by ∼30% in AD patients, but the underlying mechanisms remain elusive. ATP-binding cassette (ABC) transporters have been implicated in the regulation of Ab levels in the brain. Using new genetically modified mouse models, we show for the first time that the transporter ABCC1 has an exceptional functional impact on cerebral Ab clearance and accumulation. In mouse models, a deficiency of ABCC1 increases cerebral Aβ levels up to 12-fold, whereas activation of ABCC1 using an FDA-approved drug significantly reduces Ab load. Furthermore, we highlight functional abrogation of mitochondrial oxidative phosphorylation (OXPHOS) during aging as the important physiologic mechanism leading to ABC transporter dysfunction in elderly. Thus, by altering the temporal aggregation profile of Ab, pharmacological activation of ABC transporters and OXPHOS could impede the neurodegenerative cascade during aging that culminates in the dementia of Alzheimer's disease.
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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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".