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Anti-amyloid translation in Alzheimer's disease

CC-BY-4.0vfr_5076e7b3ff8e6b0f

id: vfr_5076e7b3ff8e6b0f
license: CC-BY-4.0
findings: 144
accepted core: 44
contested: 9

144

findings

links

125

sources

147

evidence

contested

0.63

avg conf

frontiers / frontier

Anti-amyloid translation in Alzheimer's disease

CC-BY-4.0vfr_5076e7b3ff8e6b0f

id: vfr_5076e7b3ff8e6b0f
license: CC-BY-4.0
findings: 144
accepted core: 44
contested: 9

144

findings

links

125

sources

147

evidence

contested

0.63

avg conf

Source record

back to sources

Michael Egan; James Kost; Pierre N. Tariot; Paul Aisen; Jeffrey L. Cummings; Bruno Vellas; Cyrille Sur; Yuki Mukai. New England Journal of Medicine 2018. doi:10.1056/NEJMoa1706441

id: vs_e1be38b966c19185
frontier: Anti-amyloid translation in Alzheimer's disease
year: 2018
type: paper

source boundary

frontier-owned

declared

A source record is provenance. It supports a finding only through evidence atoms, extraction spans, and reviewed finding bundles.

finding bindings

record context

2 findings

Findings bound to this source through source ids, evidence atoms, provenance, or reviewed source-record slots.

evidence atoms

materialized

1 atoms

Evidence atoms pin exact spans, measurements, selectors, or curation assertions to the source.

review context

inspectable

7 events

7 reviewable changes and 0 evaluations are attached through this source or its findings.

Locator and citation

external source

locator

doi:10.1056/NEJMoa1706441

doi

10.1056/NEJMoa1706441

pmid

29719179

imported

2026-05-06T03:57:51.843411+00:00

extraction mode

manual_curation

journal

New England Journal of Medicine

authors

Michael Egan, James Kost, Pierre N. Tariot, Paul Aisen, Jeffrey L. Cummings, Bruno Vellas, Cyrille Sur, Yuki Mukai

Caveats

No source-specific caveats are recorded.

Bound findings

Verubecestat failed to improve cognition or function in mild-to-moderate Alzheimer's disease despite BACE1 target engagement.
negative · vf_03875dbe6be66b00
Verubecestat (BACE1 inhibitor) Phase III EPOCH trial in mild-moderate AD halted for futility; cognitive worsening signal observed. Production-side amyloid intervention failed alongside MAb clearance approaches, narrowing therapeutic-window viability of the amyloid hypothesis.
therapeutic · vf_3d380bcccbe5850e

Evidence atoms

vea_3c01d09d72c7d5b1experimental · supports
Verubecestat (BACE1 inhibitor) Phase III EPOCH trial in mild-moderate AD halted for futility; cognitive worsening signal observed. Production-side amyloid intervention failed alongside MAb clearance approaches, narrowing therapeutic-window viability of the amyloid hypothesis.

Review, event, and evaluation records

events

vev_02998164eba87654finding.reviewed
Verubecestat EPOCH (Egan et al., NEJM 2018) and APECS were halted for futility, establishing BACE1 inhibition as a failed translation arm. The failed-trial finding is well-supported. Agent-drafted accept; eligible for human re-review.
agent:vela-curation-bot-2026-05-09 · 2026-05-09
vev_256faa62a301a60cfinding.reviewed
Reviewed as amyloid-pathway translation tension, not as a direct antibody contradiction.
reviewer:will-blair-bot · 2026-05-06
vev_54acd1bb09b776e3finding.caveated
BACE failures should not be treated as proof that every amyloid-lowering approach fails.
reviewer:will-blair-bot · 2026-05-06
vev_7100374369c4dbe5finding.asserted
Manual finding added to frontier state
reviewer:will-blair-bot · 2026-05-06
vev_d5fc4a90bfc01935finding.caveated
Decision-console scope: verubecestat is used here as a failed BACE program exemplar; the correction path should not generalize this single result to every amyloid-lowering approach.
reviewer:will-blair-bot · 2026-05-06
vev_e18f2033f68a422ffinding.reviewed
Reviewed for decision-console use: failed BACE program claim is scoped to verubecestat EPOCH-style clinical failure, not all anti-amyloid mechanisms.
reviewer:will-blair-bot · 2026-05-06
vev_ea98c3207e67eb18finding.asserted
Manual finding added to frontier state
reviewer:will-blair-bot · 2026-05-06

reviewable changes

vpr_02cc6836a2d1d57ffinding.review
Verubecestat EPOCH (Egan et al., NEJM 2018) and APECS were halted for futility, establishing BACE1 inhibition as a failed translation arm. The failed-trial finding is well-supported. Agent-drafted accept; eligible for human re-review.
applied · agent:vela-curation-bot-2026-05-09 · 2026-05-09
vpr_371b4e01866e4d94finding.review
Reviewed for decision-console use: failed BACE program claim is scoped to verubecestat EPOCH-style clinical failure, not all anti-amyloid mechanisms.
applied · reviewer:will-blair-bot · 2026-05-06
vpr_47e89f04337c7786finding.caveat
Decision-console scope: verubecestat is used here as a failed BACE program exemplar; the correction path should not generalize this single result to every amyloid-lowering approach.
applied · reviewer:will-blair-bot · 2026-05-06
vpr_7420a100feb4fe3ffinding.caveat
BACE failures should not be treated as proof that every amyloid-lowering approach fails.
applied · reviewer:will-blair-bot · 2026-05-06
vpr_81c389ba7649fe21finding.add
Manual finding added to frontier state
applied · reviewer:will-blair-bot · 2026-05-06
vpr_942ae202f8fa3144finding.add
Manual finding added to frontier state
applied · reviewer:will-blair-bot · 2026-05-06
vpr_da34872d64ddd2c9finding.review
Reviewed as amyloid-pathway translation tension, not as a direct antibody contradiction.
applied · reviewer:will-blair-bot · 2026-05-06

evaluations

No evaluation rows are attached.

Source record

back to sources

Michael Egan; James Kost; Pierre N. Tariot; Paul Aisen; Jeffrey L. Cummings; Bruno Vellas; Cyrille Sur; Yuki Mukai. New England Journal of Medicine 2018. doi:10.1056/NEJMoa1706441

id: vs_e1be38b966c19185
frontier: Anti-amyloid translation in Alzheimer's disease
year: 2018
type: paper

source boundary

frontier-owned

declared

A source record is provenance. It supports a finding only through evidence atoms, extraction spans, and reviewed finding bundles.

finding bindings

record context

2 findings

Findings bound to this source through source ids, evidence atoms, provenance, or reviewed source-record slots.

evidence atoms

materialized

1 atoms

Evidence atoms pin exact spans, measurements, selectors, or curation assertions to the source.

review context

inspectable

7 events

7 reviewable changes and 0 evaluations are attached through this source or its findings.

Locator and citation

external source

locator

doi:10.1056/NEJMoa1706441

doi

10.1056/NEJMoa1706441

pmid

29719179

imported

2026-05-06T03:57:51.843411+00:00

extraction mode

manual_curation

journal

New England Journal of Medicine

authors

Michael Egan, James Kost, Pierre N. Tariot, Paul Aisen, Jeffrey L. Cummings, Bruno Vellas, Cyrille Sur, Yuki Mukai

Caveats

No source-specific caveats are recorded.

Bound findings

Verubecestat failed to improve cognition or function in mild-to-moderate Alzheimer's disease despite BACE1 target engagement.
negative · vf_03875dbe6be66b00
Verubecestat (BACE1 inhibitor) Phase III EPOCH trial in mild-moderate AD halted for futility; cognitive worsening signal observed. Production-side amyloid intervention failed alongside MAb clearance approaches, narrowing therapeutic-window viability of the amyloid hypothesis.
therapeutic · vf_3d380bcccbe5850e

Evidence atoms

vea_3c01d09d72c7d5b1experimental · supports
Verubecestat (BACE1 inhibitor) Phase III EPOCH trial in mild-moderate AD halted for futility; cognitive worsening signal observed. Production-side amyloid intervention failed alongside MAb clearance approaches, narrowing therapeutic-window viability of the amyloid hypothesis.

Review, event, and evaluation records

events

vev_02998164eba87654finding.reviewed
Verubecestat EPOCH (Egan et al., NEJM 2018) and APECS were halted for futility, establishing BACE1 inhibition as a failed translation arm. The failed-trial finding is well-supported. Agent-drafted accept; eligible for human re-review.
agent:vela-curation-bot-2026-05-09 · 2026-05-09
vev_256faa62a301a60cfinding.reviewed
Reviewed as amyloid-pathway translation tension, not as a direct antibody contradiction.
reviewer:will-blair-bot · 2026-05-06
vev_54acd1bb09b776e3finding.caveated
BACE failures should not be treated as proof that every amyloid-lowering approach fails.
reviewer:will-blair-bot · 2026-05-06
vev_7100374369c4dbe5finding.asserted
Manual finding added to frontier state
reviewer:will-blair-bot · 2026-05-06
vev_d5fc4a90bfc01935finding.caveated
Decision-console scope: verubecestat is used here as a failed BACE program exemplar; the correction path should not generalize this single result to every amyloid-lowering approach.
reviewer:will-blair-bot · 2026-05-06
vev_e18f2033f68a422ffinding.reviewed
Reviewed for decision-console use: failed BACE program claim is scoped to verubecestat EPOCH-style clinical failure, not all anti-amyloid mechanisms.
reviewer:will-blair-bot · 2026-05-06
vev_ea98c3207e67eb18finding.asserted
Manual finding added to frontier state
reviewer:will-blair-bot · 2026-05-06

reviewable changes

vpr_02cc6836a2d1d57ffinding.review
Verubecestat EPOCH (Egan et al., NEJM 2018) and APECS were halted for futility, establishing BACE1 inhibition as a failed translation arm. The failed-trial finding is well-supported. Agent-drafted accept; eligible for human re-review.
applied · agent:vela-curation-bot-2026-05-09 · 2026-05-09
vpr_371b4e01866e4d94finding.review
Reviewed for decision-console use: failed BACE program claim is scoped to verubecestat EPOCH-style clinical failure, not all anti-amyloid mechanisms.
applied · reviewer:will-blair-bot · 2026-05-06
vpr_47e89f04337c7786finding.caveat
Decision-console scope: verubecestat is used here as a failed BACE program exemplar; the correction path should not generalize this single result to every amyloid-lowering approach.
applied · reviewer:will-blair-bot · 2026-05-06
vpr_7420a100feb4fe3ffinding.caveat
BACE failures should not be treated as proof that every amyloid-lowering approach fails.
applied · reviewer:will-blair-bot · 2026-05-06
vpr_81c389ba7649fe21finding.add
Manual finding added to frontier state
applied · reviewer:will-blair-bot · 2026-05-06
vpr_942ae202f8fa3144finding.add
Manual finding added to frontier state
applied · reviewer:will-blair-bot · 2026-05-06
vpr_da34872d64ddd2c9finding.review
Reviewed as amyloid-pathway translation tension, not as a direct antibody contradiction.
applied · reviewer:will-blair-bot · 2026-05-06

evaluations

No evaluation rows are attached.

vs_e1be38b966c19185 · source

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declared

2 findings

1 atoms

7 events

Bound findings

Evidence atoms

Review, event, and evaluation records

declared

2 findings

1 atoms

7 events

Bound findings

Evidence atoms

Review, event, and evaluation records