BCG vaccine awakens trained immunity against Alzheimer's in early clinical trial

BCG vaccination induces persistent trained immunity-like changes in immune cells within cerebrospinal fluid, featuring enhanced innate responsiveness and transcriptional reprogramming distinct from blood responses. In a one-year open-label trial enrolling 23 participants (12 without Alzheimer's-related pathology, 11 with), all aged 55 or older, two intradermal doses spaced one month apart proved well tolerated with no unexpected safety signals. Among participants without prior neurodegeneration, immune shifts correlated with decreased amyloid-β in cerebrospinal fluid and increased levels in blood, suggesting compartment-specific clearance. Although sample size constraints limit broad generalization, the safety profile and observed biological markers establish sufficient proof-of-concept to warrant larger controlled studies exploring whether this immune-priming strategy could mature into an early-stage neuroprotective intervention for longevity-focused clinical practice.