Falsifiable prediction from high-scoring hypothesis (score=0.725, gene=S100B). Hypothesis: Can serum S100B serve as an early biomarker of BBB dysfunction in AD, preceding amyloid/tau pathology by >3 years, and does blocking S100B-RAGE signaling prevent pericyte dysfunction? Success criteria: 1. Serum S100B is elevated >2-fold in preclinical AD (CSF p-tau181 positive, PET negative) vs age-matched controls. 2. S100B-RAGE blockade (e.g., FPS-ZM1) restores pericyte coverage (NG2+/CD31+ ratio) in 5xFAD mice by >35%. 3. BBB integrity (MRI dynamic contrast enhancement) improves by >30% after 8-week RAGE inhibitor treatment. 4. Serum S100B correlates with MRI-measured BBB leakage area (r=0.65, p<0.001) in AD cohort.