NeuroSonic Sleep Therapy: Enhancing Glymphatic Clearance of Amyloid-β Through Slow-Wave Sleep Modulation in Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease driven by amyloid-beta (Aβ), a misfolded protein forming plaques that disrupt synaptic function, drive neuronal death, and impair episodic memory encoding in the hippocampus (Vejandla et al., 2024). The failure of the glymphatic system, the brain’s perivascular waste-clearance network, removes Aβ by circulating cerebrospinal fluid (CSF) through aquaporin-4 (AQP4) channels on astrocytic endfeet into systemic circulation (Simon et al., 2022). Norepinephrine-driven arterial vasomotion (rhythmic vascular pulsations) powers this clearance, peaking during slow-wave sleep (SWS), the deepest stage of non-REM sleep (Hauglund et al., 2025). In AD, SWS disruption worsens glymphatic failure and accelerates Aβ accumulation (Wunderlin et al., 2020). While pink noise bursts synchronized to brain rhythms, named phase-locked acoustic stimulation (PLAS), can enhance SWS, its effects on Aβ clearance remain unproven (Wunderlin et al., 2023). This proposal introduces NeuroSonic Sleep Therapy (NST): slow-tempo (60-80 BPM), instrumental, low-frequency music delivered via a wearable headband aligned to each patient’s slow-wave oscillations during SWS. Unlike pink noise, NST’s musicality deepens SWS, activating limbic, prefrontal, and autonomic circuits. The resulting norepinephrine surge strengthens arterial vasomotion, elevates CSF pressure gradients through AQP4 channels, and enhances glymphatic flushing of Aβ from hippocampal tissue (Mohaupt et al., 2023).