Reactivating Brain Waste Clearance: A Novel Approach to Alzheimer’s Disease Therapy

This study aimed to investigate the extent of amyloid β (Aβ) reduction in the brain and its effects on cognitive function following the administration of a arginine vasopressin fragment AVP (4-9) analog. Seven participants (three healthy adults and four individuals with Alzheimer's disease) received an AVP (4-9) fragment analog via nasal spray for two weeks. A daily dose of 60 ng of the AVP (4-9) fragment analog was administered. We evaluated changes in Composite Biomarker (CB) levels, which reflect Aβ accumulation in the brain. Additionally, the ADAS-Cog test was conducted on the four individuals with Alzheimer's disease before and after administration. A 5- to 20-fold difference in CB levels was observed between healthy adults and individuals with Alzheimer's disease. Among individuals with Alzheimer's disease, CB levels decreased by an average of 36% following AVP (4-9) fragment analog administration. The AVP (4-9) fragment analog resulted in a reduction in CB values without significant differences between individuals with Alzheimer's disease and healthy individuals. The ADAS-Cog test showed an average improvement of 8.1 points in cognitive function. No adverse events were observed. The AVP (4-9) fragment and its analogs, which act as agonists of the vasopressin 1a receptor (V1aR), represent a promising therapeutic approach for Alzheimer's disease by enhancing the brain's waste clearance system and improving cognitive function. This dual-action therapeutic strategy addresses the limitations of existing treatments and holds potential as a groundbreaking therapeutic option for neurodegenerative diseases. Further large-scale studies are required to confirm the efficacy and safety of this novel treatment strategy.