Pre-pilot study: Reactivating brain waste clearance via vasopressin fragment—A novel approach to Alzheimer's disease therapy

Background Impaired clearance of amyloid-β (Aβ) and other metabolic waste products has been implicated in Alzheimer's disease (AD). Arginine vasopressin (AVP) fragments have been associated with memory-related effects and may influence glymphatic-related pathways. Objective This pre-pilot exploratory study investigated the potential effects of an AVP (4–9) fragment analog on Aβ-related biomarkers and cognitive function. Methods Seven participants (three healthy adults and four individuals with AD) received intranasal administration of an AVP (4–9) fragment analog for two weeks at a daily dose of 60 ng. Aβ-related burden was assessed using blood-based Composite Biomarker (CB) values reported to correlate with amyloid PET findings. Cognitive function in AD participants was evaluated using the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog). Results At baseline, CB values were 5- to 20-fold higher in individuals with AD than in healthy adults. Following treatment, mean CB values in the AD group decreased by 36%, with comparable relative reductions observed across groups. ADAS-Cog scores improved by a mean of 8.1 points over two weeks. No adverse events were observed. Conclusions AVP (4–9) fragments may influence cognitive processes and glymphatic-related pathways. These findings should be interpreted cautiously given the small sample size and open-label design but may provide a basis for future controlled investigations.