Accumulation of amyloid-beta is the primary causal driver of Alzheimer's disease pathogenesis
Weak-link patterns
Brief §8's named failure modes, computed from this claim's own paper roles and status -- not a single weakness score. Patterns B and E aren't implemented yet (need dependency-graph machinery, docs/BASIC_ROADMAP.md Phase 11).
stored status is 'unknown_conflicting'
flagship 'Alzheimer's Disease: The Amyloid Cascade Hypothesis' (7507 citations) vs 4 contradicting row(s) of 11 total (needs >=3 contradicting)
Open questions
Pattern G. Human-written, never generated -- deliberately no importance or priority score (docs/BASIC_ROADMAP.md's own precedent against inventing one, matching innovation_considerations).
Is amyloid-beta accumulation the primary causal driver of Alzheimer's, or a downstream marker of the real cause -- given repeated Phase 3 trial failures directly targeting it?
Motivated by: Pattern C (conflicting evidence) and Pattern F (highly-cited original, 4 later contradicting trial results)
Evidence map
Position shows direction, circle area shows citation count. Click a paper for the reason its role was assigned.
Evidence dimensions
Eight independent 0–5 judgments, each with a written rationale. Deliberately never summed into one score.
Enormous, high-quality and directly on point, with genuinely strong human-genetic evidence for a causal role - but the therapeutic tests that should follow from 'primary driver' mostly failed, and the two that succeeded did so modestly.
Among the most intensively tested hypotheses in modern biomedicine, across three decades and many independent groups.
Strictly per the same-paradigm definition: no independent re-run of the 1992 synthesis as such. Essentially all subsequent work is different-method, which the triangulation dimension covers instead.
Why this status
The derivation rule, evaluated top to bottom, first match wins. This is the rule itself — not a confidence score standing in for one.
1 retracted paper is excluded from every count below, so the rules weigh 11 of the 12 papers listed above. A retraction means the finding was withdrawn — the row stays visible, but it is not evidence.
- 1Unknown — unexplored
11 paper rows (needs <3) and evidence_strength=3 (needs <=1); both required
- 2Unknown — conflicting evidencematched
(a) 0 failure vs 0 success rows -> no; (b) 3 review rows — opposite-verdict test is a human judgment, not a count; (c) 4 conceptual failure vs 3 conceptual success, 1 original -> fires (balanced)
- 3Unknown — underdeterminednot reached
alternative_explanations=2 (needs <=1) AND evidence_strength=3 (needs >=3)
- 4Establishednot reached
independent_replication=1 (>=4), evidence_strength=3 (>=4), consensus=3 (>=4)
Recorded rationale
v4 rule 2 - clause (c1) fires on a balanced 4-vs-4 split of conceptual replications (four phase 3 anti-amyloid trials confirming vs four failing), and clause (b) fires on reviews reaching opposite verdicts (Selkoe & Hardy 2016 vs Herrup 2015 and Kepp 2023). Naive citation-only guess was 'established'; divergence material. Pilot 4 (biomedicine; prior familiarity disclosed HIGH). NOTE: one conceptual_replication_success row (Lesne 2006, W2075481535) is formally RETRACTED and is nonetheless counted as supporting evidence - the rubric has no retraction provision. See Pilot 4 log Finding 1 and the proposed v5 correction. Excluding it leaves the status unchanged here (3 vs 4 is still within 1), but a worked counterexample in the log shows cases where it would flip.