biostudies-literatureMurdock MHNCCIH NIH HHSNIA NIH HHSNIDA NIH HHSNIMH NIH HHSNINDS NIH HHS149-156https://www.ebi.ac.uk/biostudies/studies/S-EPMC10917684biostudies-literatureUnknown627(8002)The glymphatic movement of fluid through the brain removes metabolic waste^1-4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease^5-8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer's disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.NatureMultisensory gamma stimulation promotes glymphatic clearance of amyloid.PMC10917684R01 AT011460R01 DA029639R01 AG069232R01 MH114031R01 DA045549R01 NS051874R01 MH122971R37 NS051874Islam MRSneve MGaliana FAkay LAVictor MBLai CKopell NMcCarthy MMSun NWang SPao PCLavoie NSYang CYMurdock MHKahn MCLeary NPiatkevich KDBlanco-Duque CKellis MKim TBubnys ABoyden ESQian YTsai LHMa EfalseMultisensory gamma stimulation promotes glymphatic clearance of amyloid.The glymphatic movement of fluid through the brain removes metabolic waste^1-4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease^5-8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer's disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.2024-01-01T00:00:00Z2024 Mar2025-04-18T15:28:00.444Z2025-04-07T02:10:03.913ZS-EPMC109176843841887610.1038/s41586-024-07132-6