2. Academic Validation
  3. Multisensory gamma stimulation promotes glymphatic clearance of amyloid

Multisensory gamma stimulation promotes glymphatic clearance of amyloid

  • Nature. 2024 Mar;627(8002):149-156. doi: 10.1038/s41586-024-07132-6.
Mitchell H Murdock 1,  Cheng-Yi Yang 1,  Na Sun 2 3,  Ping-Chieh Pao 1,  Cristina Blanco-Duque 1,  Martin C Kahn 1,  TaeHyun Kim 1,  Nicolas S Lavoie 1,  Matheus B Victor 1,  Md Rezaul Islam 1,  Fabiola Galiana 1,  Noelle Leary 1,  Sidney Wang 1,  Adele Bubnys 1,  Emily Ma 1,  Leyla A Akay 1,  Madison Sneve 4 5 6,  Yong Qian 4 5 6,  Cuixin Lai 7,  Michelle M McCarthy 8,  Nancy Kopell 8,  Manolis Kellis 2 3,  Kiryl D Piatkevich 4 5 6 7,  Edward S Boyden 4 5 6,  Li-Huei Tsai 9 10
Affiliations

Affiliations

  • 1 Department of Brain and Cognitive Sciences and the Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 2 MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA.
  • 3 Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • 4 Departments of Biological Engineering and Brain and Cognitive Sciences, McGovern Institute, Cambridge, MA, USA.
  • 5 Koch Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 6 Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 7 School of Life Sciences, Westlake University, Westlake Laboratory of Life Sciences and Biomedicine, and Westlake Institute for Advanced Study, Hangzhou, China.
  • 8 Department of Mathematics and Statistics, Boston University, Boston, MA, USA.
  • 9 Department of Brain and Cognitive Sciences and the Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected].
  • 10 Broad Institute of MIT and Harvard, Cambridge, MA, USA. [email protected].
PMID: 38418876 DOI: 10.1038/s41586-024-07132-6
Abstract

The glymphatic movement of fluid through the brain removes metabolic waste1-4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease5-8. 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.

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