Multisensory gamma stimulation promotes glymphatic clearance of amyloid

• 成果类型: Article
• 署名作者: Murdock, Mitchell H.; Yang, Cheng-Yi; Sun, Na; Pao, Ping-Chieh; Blanco-Duque, Cristina; Kahn, Martin C.; Kim, TaeHyun; Lavoie, Nicolas S.; Victor, Matheus B.; Islam, Md Rezaul; Galiana, Fabiola; Leary, Noelle; Wang, Sidney; Bubnys, Adele; Ma, Emily; Akay, Leyla A.; Sneve, Madison; Qian, Yong; Lai, Cuixin; McCarthy, Michelle M.; Kopell, Nancy; Kellis, Manolis; Piatkevich, Kiryl D.; Boyden, Edward S.; Tsai, Li-Huei
• 署名单位: Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Westlake Laboratory; Westlake University; Westlake University; Boston University
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6190
• DOI: 10.1038/s41586-024-07132-6
• 发表日期: 2024-03-07
• 页码: 149-+
• 关键词: vasoactive intestinal polypeptide; alzheimer-disease; aquaporin-4; localization; entrainment; cortex

摘要

The glymphatic movement of fluid through the brain removes metabolic waste(1-4). Noninvasive 40Hz stimulation promotes 40Hz 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 40Hz 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.