The amyloid cascade hypothesis: an updated critical review
Bibliographic record
Abstract
Results from recent clinical trials of antibodies that target amyloid-β (Aβ) for Alzheimer's disease have created excitement and have been heralded as corroboration of the amyloid cascade hypothesis. However, while Aβ may contribute to disease, genetic, clinical, imaging and biochemical data suggest a more complex aetiology. Here we review the history and weaknesses of the amyloid cascade hypothesis in view of the new evidence obtained from clinical trials of anti-amyloid antibodies. These trials indicate that the treatments have either no or uncertain clinical effect on cognition. Despite the importance of amyloid in the definition of Alzheimer's disease, we argue that the data point to Aβ playing a minor aetiological role. We also discuss data suggesting that the concerted activity of many pathogenic factors contribute to Alzheimer's disease and propose that evolving multi-factor disease models will better underpin the search for more effective strategies to treat the 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 | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.005 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".