Vasomechanic treatment increases efflux of human brain proteins

Abstract An age-related decline in vasodilation mediated by neurovascular nitric oxide (NO) and vasoconstriction driven by the Piezo1 receptor precede the aggregation of soluble brain proteins such as amyloid-β (Aβ), which then causes further disruption of brain solute homeostasis, ultimately leading to neurodegeneration in Alzheimer’s disease. Preclinical studies show that restoring these vascular functions increases neurofluidic efflux and improves cognitive outcomes. Here, we tested effects of sublingual NO and/or Piezo1 receptor-targeted mechanotransductive whole-body vibrations (WBV p ) in healthy adults (n = 29) on brain fluid dynamics and CNS-to-blood protein efflux using multimodal neuroimaging and blood biomarker analysis. The combined vasomechanic interventions (NO+WBV p ) produced a synergistic enhancement of brain fluid transport and markedly increased the efflux of soluble brain-derived proteins (Aβ 40&42 , glial fibrillary acidic protein) into the bloodstream. The effects increase with age and the magnitude of NO-induced hypotension. Importantly, the combined intervention was well-tolerated, with no severe adverse physiological responses. Results demonstrate that a simple, non-invasive vasomechanic intervention can transiently promote brain-to-blood protein clearance in humans, highlighting a potentially safe and accessible therapeutic avenue for neurodegenerative conditions characterized by impaired brain solute removal and protein aggregation.