Pericyte coverage loss is an early event in BBB breakdown preceding neurodegeneration, and sPDGFRβ shed from damaged pericytes serves as a peripheral indicator of this process. If plasma sPDGFRβ reflects ongoing BBB pericyte loss independently of amyloid and tau, it could provide a practical blood-based screening tool for pre-dementia intervention. This challenge requires: (1) validating the sPDGFRβ threshold in two independent prospective cohorts, (2) demonstrating independence from Aβ42/p-tau181/NfL, and (3) establishing that the signal reflects pericyte coverage (not other PDGFRβ-expressing cells). Falsifiable prediction: sPDGFRβ AUC for 3-year MCI-to-dementia conversion should be ≥0.75 in ADNI-3 (n ≥ 200 MCI subjects) and replicated in BioFINDER-2. Inclusion of sPDGFRβ in a base model (age, sex, APOE4) should add ≥0.05 AUC over the base model alone.