Description
What blood-brain barrier permeability changes serve as early biomarkers for neurodegeneration, and what CSF/blood biomarker panels can detect them?
Resolution criteria
Resolution requires: (1) Prospective longitudinal MRI study with DCE-MRI or gadolinium leakage mapping in cognitively normal participants (n>=100) showing BBB Ktrans or Vp elevation >=2 years before tau/amyloid PET threshold positivity, establishing early biomarker precedence; (2) Matched CSF and plasma biomarker panel (soluble PDGFR-beta, tight-junction fragments claudin-5/occludin, matrix metalloproteinases MMP-2/9) with AUC>=0.75 for early neurodegeneration detection in an independent validation cohort (n>=80); (3) Regional specificity: BBB breakdown hotspots (hippocampus, entorhinal cortex, locus coeruleus) correlate with subsequent atrophy measured by structural MRI (r>=0.5). Cross-sectional case-control BBB comparisons without longitudinal precedence data are insufficient.