What does it take to calibrate fluid and imaging biomarkers against clinical decline in early Alzheimer's disease?

Findings, by impact.

Each row is a draft finding. The cross-frontier link count is the number of typed dependency links to anti-amyloid or BBB child findings. A reviewer's promote-to-accepted-core decision lives in /review/promote/{finding_id} on the local Workbench.

• vf_439b33c0ec425686 · accepted · 3 cross-frontier
  Hippocampal blood-brain barrier breakdown measured by DCE-MRI Ktrans is elevated in individuals with early cognitive dysfunction independent of amyloid and tau status, supporting BBB permeability as an early-stage biomarker of cognitive dec...
• vf_84ebd5a5ef97eba6 · accepted · 2 cross-frontier
  Donanemab efficacy on iADRS at 76 weeks is larger in the low or medium tau pathology stratum (LSM difference 3.25, 95% CI 1.88-4.62) than in the combined low/medium plus high tau population (LSM difference 2.92, 95% CI 1.51-4.33), supportin...
• vf_1731753d816fb7d0 · accepted · 1 cross-frontier
  In TRAILBLAZER-ALZ 2, donanemab slowed CDR-SB progression by 0.67 points at 76 weeks vs placebo in early symptomatic Alzheimer disease participants with low or medium tau pathology (CDR-SB difference -0.67, 95% CI -0.95 to -0.40, P<.001).
• vf_572f67e17d14dd9b · accepted · 1 cross-frontier
  The minimum clinically important difference (MCID) for CDR-SB in early Alzheimer disease serves as the calibration anchor for biomarker-to-clinical-decline mapping in this frontier; biomarker movements are evaluated against this threshold r...
• vf_30c1be51b40e4c81 · accepted · 0 cross-frontier
  Plasma p-tau181 rises across the Alzheimer disease continuum from cognitively unimpaired through symptomatic stages, with elevation appearing before clinical symptom onset and tracking the spatiotemporal progression of AD-characteristic pat...
• vf_3f801642feaf736a · accepted · 0 cross-frontier
  Cognitively unimpaired individuals positive for both amyloid and tau on PET (A+T+) are at substantially elevated short-term risk of cognitive decline and progression to mild cognitive impairment compared to A+T- and A-T- individuals.
• vf_8b47d4846c86bc8f · accepted · 0 cross-frontier
  The Centiloid Project standardizes quantitative amyloid PET measures across tracers and centers by anchoring the scale to 0 (typical young controls) and 100 (typical Alzheimer disease), enabling cross-tracer and cross-cohort comparability o...
• vf_8f2d8f546976dcb3 · accepted · 0 cross-frontier
  Cerebrospinal fluid amyloid-β42, total tau, and phosphorylated tau form the foundational fluid biomarker triad for Alzheimer disease, with detection of disease-related changes possible years before clinical symptom onset.
• vf_fe811725a53f0ed9 · accepted · 0 cross-frontier
  Fully automated Elecsys CSF assays of amyloid-β1-42, total tau, and phosphorylated tau ratios concord with amyloid PET reference status across BioFINDER (n=277) and ADNI (n=646) cohorts and predict clinical progression in mild cognitive imp...

Cross-frontier bridges.

The frontier declares dependencies on the anti-amyloid translation frontier and the BBB child frontier; typed links from local findings reference target findings on those peers by vf_id@vfr_id. The deps live in frontier.yaml under dependencies.frontiers_v2 (a v0.59 schema addition that fixed the split-repo loader gap).

• anti-amyloid-translation · vfr_5076e7b3ff8e6b0f
  snapshot b1ecc2128a5e813d…
  locator file:///Users/williamblair/personal/vela/projects/anti-amyloid-translation/frontier.json
• alzheimers-bbb-dysfunction-delivery · vfr_bbbd20260507c001
  snapshot 18fd3dbabd0e08e9…
  locator file:///Users/williamblair/personal/vela/projects/alzheimers-bbb-dysfunction-delivery/frontier.json

7 typed cross-frontier links land between the local findings and the two peer frontiers. Linked targets cover the MCID-for-CDR-SB scope anchor in anti-amyloid, the anti-amyloid efficacy/safety meta-analysis, the pericyte-deficiency mechanism in the BBB child, the BBB-AD biomarker interaction analysis, and the DCE-MRI BBB leakage spatial pattern. A reviewer promotes those links to accepted-core when the underlying findings are themselves promoted.

Reproduce.

# Re-run the full pipeline offline against the materialized frontier:
./scripts/build-early-ad-impact-examples.sh

# Re-fetch the source dossier (cache-first; no network unless --refresh):
for ident in $(jq -r '.sources[].identifier' projects/early-ad-biomarker-calibration/sources/source-dossier.v0.1.json); do
  vela source-fetch "$ident" --cache projects/early-ad-biomarker-calibration --json > /dev/null
done

# Inspect a single finding's impact:
vela impact projects/early-ad-biomarker-calibration vf_1731753d816fb7d0 --json

Status.

This frontier is at the seed-and-bridge stage. The next review wave promotes some draft findings to accepted-core through the local Workbench, declares additional bridges, and writes an review/review-packet.v1.json with the verdict trail. The substrate is doctrine-clean: vela check --strict reports proof_readiness: needs_review because no finding has been promoted yet, which is the honest state for a frontier with no reviewed verdicts.

Inspect the repo at projects/early-ad-biomarker-calibration/ .