{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:16:08Z","timestamp":1790162168138,"version":"4.1.0"},"reference-count":130,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The glymphatic system, a cerebral waste clearance pathway identified over a decade ago, has reshaped understanding of Alzheimer\u2019s disease (AD) pathogenesis by linking impaired brain homeostasis to amyloid-\u03b2 and tau accumulation. This review synthesizes the biological mechanisms governing glymphatic function, including arterial pulsation, vasomotion, cerebrospinal fluid turnover, norepinephrine oscillations, aquaporin-4 polarization, and meningeal lymphatic drainage, and evaluates emerging non-invasive modulation strategies. Unlike immunotherapies that directly target pathological proteins with risks of amyloid-related imaging abnormalities, non-invasive approaches offer a new perspective, shifting from a target-and-eliminate strategy toward a restore-and-maintain strategy of endogenous clearance. A key insight is that therapeutic efficacy may depend more on engaging multiple mechanistic pathways concurrently than on the specific technology. Notably, preliminary evidence from small exploratory subgroup analyses suggests that APOE\u03f54 carriers, despite exhibiting poorer baseline glymphatic function, may show differential responsiveness to certain non-invasive interventions, though these findings are hypothesis-generating and require independent replication in larger, prespecified trials. This review establishes a multidimensional evaluation framework spanning principles, mechanisms, and clinical evidence, providing theoretical support to accelerate translation of these promising strategies into AD therapeutics.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1884893","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T10:54:07Z","timestamp":1790160847000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting glymphatic-associated pathways for Alzheimer\u2019s disease: a review of non-invasive modulation strategies, mechanisms, and emerging evidence"],"prefix":"10.3389","volume":"17","author":[{"given":"Junyu","family":"Chen","sequence":"first","affiliation":[{"name":"Zhongshan School of Medicine, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Heze Medical College","place":["Heze, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Brain Science, Institute of Brain Science and Brain-inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences","place":["Jinan, China"]},{"name":"Shandong Institute of Brain Science and Brain-inspired Research","place":["Jinan, China"]},{"name":"Department of Geriatric Medicine, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)32205-4","article-title":"Alzheimer's disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"15056","DOI":"10.1038\/nrdp.2015.56","article-title":"Alzheimer's disease","volume":"1","author":"Masters","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"B3","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer's disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nature23002","article-title":"Cryo-EM structures of tau filaments from Alzheimer's disease","volume":"547","author":"Fitzpatrick","year":"2017","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07680-x","article-title":"CryoET of \u03b2-amyloid and tau within postmortem Alzheimer's disease brain","volume":"631","author":"Gilbert","year":"2024","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/s1474-4422(20)30412-9","article-title":"ApoE and Alzheimer's disease: Advances in genetics, pathophysiology, and therapeutic approaches","volume":"20","author":"Serrano-Pozo","year":"2021","journal-title":"Lancet Neurol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"14794","DOI":"10.3390\/ijms241914794","article-title":"Amyloid precursor protein and Alzheimer's disease","volume":"24","author":"Orobets","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-025-00465-w","article-title":"Second-generation anti-amyloid monoclonal antibodies for Alzheimer's disease: Current landscape and future perspectives","volume":"14","author":"Kim","year":"2025","journal-title":"Transl Neurodegener"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1016\/s0140-6736(22)02480-1","article-title":"Lecanemab for Alzheimer's disease: Tempering hype and hope","volume":"400","year":"2022","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early Alzheimer's disease","volume":"388","author":"van Dyck","year":"2023","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nature19323","article-title":"The antibody aducanumab reduces A\u03b2 plaques in Alzheimer's disease","volume":"537","author":"Sevigny","year":"2016","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"197","DOI":"10.14283\/jpad.2022.30","article-title":"Two randomized phase 3 studies of aducanumab in early Alzheimer's disease","volume":"9","author":"Budd Haeberlein","year":"2022","journal-title":"J Prev Alzheimers Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0624-8","article-title":"Disease-associated astrocytes in Alzheimer's disease and aging","volume":"23","author":"Habib","year":"2020","journal-title":"Nat Neurosci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0439-0","article-title":"Aquaporin-4 as a new target against methamphetamine-induced brain alterations: Focus on the neurogliovascular unit and motivational behavior","volume":"55","author":"Leit\u00e3o","year":"2018","journal-title":"Mol Neurobiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-020-2283-0","article-title":"Epigenetic regulation of amyloid-beta metabolism in Alzheimer's disease","volume":"40","author":"He","year":"2020","journal-title":"Curr Med Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/s1474-4422(18)30450-2","article-title":"Implications of sleep disturbance and inflammation for Alzheimer's disease dementia","volume":"18","author":"Irwin","year":"2019","journal-title":"Lancet Neurol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118627","article-title":"Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease","volume":"264","author":"Kesika","year":"2021","journal-title":"Life Sci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"147ra11","DOI":"10.1126\/scitranslmed.3003748","article-title":"A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \u03b2","volume":"4","author":"Iliff","year":"2012","journal-title":"Sci Transl Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nature14432","article-title":"Structural and functional features of central nervous system lymphatic vessels","volume":"523","author":"Louveau","year":"2015","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.neuron.2017.07.030","article-title":"The neurovascular unit coming of age: A journey through neurovascular coupling in health and disease","volume":"96","author":"Iadecola","year":"2017","journal-title":"Neuron"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.17-01-00171.1997","article-title":"Specialized membrane domains for water transport in glial cells: High-resolution immunogold cytochemistry of aquaporin-4 in rat brain","volume":"17","author":"Nielsen","year":"1997","journal-title":"J Neurosci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/jci67677","article-title":"Brain-wide pathway for waste clearance captured by contrast-enhanced MRI","volume":"123","author":"Iliff","year":"2013","journal-title":"J Clin Invest"},{"key":"B23","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/s41467-026-68374-8","article-title":"The glymphatic system clears amyloid beta and tau from brain to plasma in humans","volume":"17","author":"Dagum","year":"2026","journal-title":"Nat Commun"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0368-8","article-title":"Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease","volume":"560","author":"Da Mesquita","year":"2018","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe4601","article-title":"Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and \u03b2-amyloid pathology","volume":"7","author":"Da Mesquita","year":"2021","journal-title":"Sci Adv"},{"key":"B26","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s40478-022-01498-2","article-title":"Sleep fragmentation affects glymphatic system through the different expression of AQP4 in wild type and 5xFAD mouse models","volume":"11","author":"Vasciaveo","year":"2023","journal-title":"Acta Neuropathol Commun"},{"key":"B27","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.cell.2024.11.027","article-title":"Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep","volume":"188","author":"Hauglund","year":"2025","journal-title":"Cell"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70837","article-title":"APOE4 modulates the association between DTI-ALPS index and Alzheimer's pathologies","volume":"21","author":"Kang","year":"2025","journal-title":"Alzheimers Dement"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24271","article-title":"Impairment of paravascular clearance pathways in the aging brain","volume":"76","author":"Kress","year":"2014","journal-title":"Ann Neurol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-026-02261-9","article-title":"Amyloid-\u03b2-driven glymphatic dysfunction in Alzheimer's disease model mice is driven by Ca(2+)-mediated increases in astrocytic cholesterol","volume":"29","author":"Zhang","year":"2026","journal-title":"Nat Neurosci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/cns.70810","article-title":"Glymphatic system dysfunction in central nervous system diseases","volume":"32","author":"Zahran","year":"2026","journal-title":"CNS Neurosci Ther"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.1592-13.2013","article-title":"Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain","volume":"33","author":"Iliff","year":"2013","journal-title":"J Neurosci"},{"key":"B33","doi-asserted-by":"publisher","first-page":"4878","DOI":"10.1038\/s41467-018-07318-3","article-title":"Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension","volume":"9","author":"Mestre","year":"2018","journal-title":"Nat Commun"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.788519","article-title":"Impaired glymphatic function and pulsation alterations in a mouse model of vascular cognitive impairment","volume":"13","author":"Li","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-02073-3","article-title":"Region-specific drivers of CSF mobility measured with MRI in humans","volume":"28","author":"Hirschler","year":"2025","journal-title":"Nat Neurosci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114977","article-title":"Sleep deprivation leads to non-adaptive alterations in sleep microarchitecture and amyloid-\u03b2 accumulation in a murine Alzheimer model","volume":"43","author":"Cankar","year":"2024","journal-title":"Cell Rep"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.5029","article-title":"Cerebrospinal fluid turnover as a driver of brain clearance","volume":"37","author":"Smets","year":"2024","journal-title":"NMR BioMed"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.932469","article-title":"CSF circulation and dispersion yield rapid clearance from intracranial compartments","volume":"10","author":"Hornkj\u00f8l","year":"2022","journal-title":"Front Bioeng Biotechnol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.212400","article-title":"Choroid plexus volume and permeability at brain MRI within the Alzheimer disease clinical spectrum","volume":"304","author":"Choi","year":"2022","journal-title":"Radiology"},{"key":"B40","doi-asserted-by":"publisher","first-page":"4411","DOI":"10.1038\/s41467-020-18115-2","article-title":"Circadian control of brain glymphatic and lymphatic fluid flow","volume":"11","author":"Hablitz","year":"2020","journal-title":"Nat Commun"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c10519","article-title":"Engineering near-infrared-II nanoprobes reveal dexmedetomidine potentiating brain waste clearance in healthy and sleep-restricted mice","volume":"19","author":"Sun","year":"2025","journal-title":"ACS Nano"},{"key":"B42","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41398-018-0094-x","article-title":"Genetic variation in aquaporin-4 moderates the relationship between sleep and brain A\u03b2-amyloid burden","volume":"8","author":"Rainey-Smith","year":"2018","journal-title":"Transl Psychiatry"},{"key":"B43","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s12987-023-00445-0","article-title":"Pulsatile cerebral paraarterial flow by peristalsis, pressure and directional resistance","volume":"20","author":"Sharp","year":"2023","journal-title":"Fluids Barriers CNS"},{"key":"B44","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s12987-022-00366-4","article-title":"Mathematical modelling of the CSF system: Effects of microstructures and posture on optic nerve subarachnoid space dynamics","volume":"19","author":"Holmlund","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"B45","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41467-021-27887-0","article-title":"Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes","volume":"13","author":"Albayram","year":"2022","journal-title":"Nat Commun"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142290","article-title":"A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules","volume":"212","author":"Aspelund","year":"2015","journal-title":"J Exp Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0312-x","article-title":"Dural lymphatics regulate clearance of extracellular tau from the CNS","volume":"14","author":"Patel","year":"2019","journal-title":"Mol Neurodegener"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12656","article-title":"Deep cervical lymph node ligation aggravates AD-like pathology of APP\/PS1 mice","volume":"29","author":"Wang","year":"2019","journal-title":"Brain Pathol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20220618","article-title":"Arachnoid granulations are lymphatic conduits that communicate with bone marrow and dura-arachnoid stroma","volume":"220","author":"Shah","year":"2023","journal-title":"J Exp Med"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1038\/s41467-017-01484-6","article-title":"Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice","volume":"8","author":"Ma","year":"2017","journal-title":"Nat Commun"},{"key":"B51","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s40478-021-01198-3","article-title":"Repetitive transcranial magnetic stimulation increases the brain's drainage efficiency in a mouse model of Alzheimer's disease","volume":"9","author":"Lin","year":"2021","journal-title":"Acta Neuropathol Commun"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2140524","article-title":"Continuous theta-burst stimulation promotes paravascular csf-interstitial fluid exchange through regulation of aquaporin-4 polarization in app\/ps1 mice","volume":"2022","author":"Wu","year":"2022","journal-title":"Mediators Inflammation"},{"key":"B53","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1186\/s12984-025-01738-1","article-title":"Effects of intermittent theta-burst stimulation on cognition and glymphatic system activity in mild cognitive impairment and very mild Alzheimer's disease: A randomized controlled trial","volume":"22","author":"Yang","year":"2025","journal-title":"J NeuroEng Rehabil"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1177\/13872877251366656","article-title":"Effects of cerebellar intermittent theta-burst stimulation on patients with Alzheimer's disease: A randomized controlled trial","volume":"107","author":"Zhang","year":"2025","journal-title":"J Alzheimers Dis"},{"key":"B55","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/s0165-6147(00)89058-6","article-title":"Neurosteroids and gabaa receptor function","volume":"16","author":"Lambert","year":"1995","journal-title":"Trends Pharmacol Sci"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15869","article-title":"Gaba promotes interstitial fluid clearance in an aqp4-dependent manner by activating the gaba(a) r","volume":"166","author":"Wu","year":"2023","journal-title":"J Neurochem"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2020.135197","article-title":"Continuous theta burst stimulation dilates meningeal lymphatic vessels by up-regulating vegf-c in meninges","volume":"735","author":"Li","year":"2020","journal-title":"Neurosci Lett"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170391","article-title":"Development and plasticity of meningeal lymphatic vessels","volume":"214","author":"Antila","year":"2017","journal-title":"J Exp Med"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2025.1597311","article-title":"The glymphatic system as a therapeutic target: tms-induced modulation in older adults","volume":"17","author":"Sundman","year":"2025","journal-title":"Front Aging Neurosci"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2023.04.001","article-title":"The impact of gamma transcranial alternating current stimulation (tacs) on cognitive and memory processes in patients with mild cognitive impairment or Alzheimer's disease: A literature review","volume":"16","author":"Nissim","year":"2023","journal-title":"Brain Stimul"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2025.1549230","article-title":"Preclinical insights into gamma-tacs: Foundations for clinical translation in neurodegenerative diseases","volume":"19","author":"S\u00e1nchez-Garrido Campos","year":"2025","journal-title":"Front Neurosci"},{"key":"B62","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s40035-024-00423-y","article-title":"Transcranial alternating current stimulation (tacs) at gamma frequency: An up-and-coming tool to modify the progression of Alzheimer's disease","volume":"13","author":"De Paolis","year":"2024","journal-title":"Transl Neurodegener"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2025.1565881","article-title":"Individualized frequency and montage tacs to engage theta-gamma coupling and enhance working memory in mild cognitive impairment","volume":"16","author":"Mirjalili","year":"2025","journal-title":"Front Psychiatry"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26411","article-title":"Increasing brain gamma activity improves episodic memory and restores cholinergic dysfunction in Alzheimer's disease","volume":"92","author":"Benussi","year":"2022","journal-title":"Ann Neurol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.46556","article-title":"Home-based gamma transcranial alternating current stimulation in patients with Alzheimer disease: A randomized clinical trial","volume":"8","author":"Cantoni","year":"2025","journal-title":"JAMA Netw Open"},{"key":"B66","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s13195-021-00922-4","article-title":"Impact of multisession 40hz tacs on hippocampal perfusion in patients with Alzheimer's disease","volume":"13","author":"Sprugnoli","year":"2021","journal-title":"Alzheimers Res Ther"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.241463","article-title":"Modulation of cortical and hippocampal functional mri connectivity following transcranial alternating current stimulation in mild Alzheimer disease","volume":"315","author":"Wang","year":"2025","journal-title":"Radiology"},{"key":"B68","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s13195-024-01570-0","article-title":"Transcranial alternating current stimulation for patients with mild Alzheimer's disease (transform-ad): A randomized controlled clinical trial","volume":"16","author":"Tang","year":"2024","journal-title":"Alzheimers Res Ther"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2023.1168673","article-title":"Tele-supervised home-based transcranial alternating current stimulation (tacs) for Alzheimer's disease: A pilot study","volume":"17","author":"Cappon","year":"2023","journal-title":"Front Hum Neurosci"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.26559","article-title":"A new perspective for evaluating the efficacy of tacs and tdcs in improving executive functions: A combined tes and fnirs study","volume":"45","author":"Lu","year":"2024","journal-title":"Hum Brain Mapp"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07132-6","article-title":"Multisensory gamma stimulation promotes glymphatic clearance of amyloid","volume":"627","author":"Murdock","year":"2024","journal-title":"Nature"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2021.739333","article-title":"40-hz blue light changes hippocampal activation and functional connectivity underlying recognition memory","volume":"15","author":"Lin","year":"2021","journal-title":"Front Hum Neurosci"},{"key":"B73","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/s41421-024-00701-z","article-title":"40 hz light flickering facilitates the glymphatic flow via adenosine signaling in mice","volume":"10","author":"Sun","year":"2024","journal-title":"Cell Discov"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1042\/bj3280739","article-title":"Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta","volume":"328","author":"Griffiths","year":"1997","journal-title":"Biochem J"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1038\/nature18966","article-title":"Structure of the adenosine a(2a) receptor bound to an engineered g protein","volume":"536","author":"Carpenter","year":"2016","journal-title":"Nature"},{"key":"B76","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41467-024-55678-w","article-title":"Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer's disease","volume":"16","author":"Wu","year":"2025","journal-title":"Nat Commun"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-023-00920-1","article-title":"40 hz light flickering promotes sleep through cortical adenosine signaling","volume":"34","author":"Zhou","year":"2024","journal-title":"Cell Res"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.12965\/jer.2244042.021","article-title":"Exercise with 40-hz light flicker improves hippocampal insulin signaling in Alzheimer disease mice","volume":"18","author":"Kim","year":"2022","journal-title":"J Exerc Rehabil"},{"key":"B79","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s13195-020-00631-4","article-title":"Physical exercise during exposure to 40-hz light flicker improves cognitive functions in the 3xtg mouse model of Alzheimer's disease","volume":"12","author":"Park","year":"2020","journal-title":"Alzheimers Res Ther"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00751.2021","article-title":"Combined effects of aerobic exercise and 40-hz light flicker exposure on early cognitive impairments in Alzheimer's disease of 3\u00d7tg mice","volume":"132","author":"Park","year":"2022","journal-title":"J Appl Physiol (1985)"},{"key":"B81","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1038\/s41467-023-37685-5","article-title":"Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders","volume":"14","author":"Eide","year":"2023","journal-title":"Nat Commun"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0326881","article-title":"Transcranial photobiomodulation therapy with 808\u2009nm light changes expression of genes and proteins associated with neuroprotection, neuroinflammation, oxidative stress, and Alzheimer's disease: Whole rna sequencing of mouse cortex and hippocampus","volume":"20","author":"Li","year":"2025","journal-title":"PloS One"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.366499","article-title":"Transcranial photobiomodulation with near-infrared light: A promising therapeutic modality for Alzheimer's disease","volume":"18","author":"Liu","year":"2023","journal-title":"Neural Regener Res"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2025.102988","article-title":"Modulating cerebrospinal fluid dynamics using pulsed photobiomodulation","volume":"19","author":"Motsenyat","year":"2026","journal-title":"Brain Stimul"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1364\/boe.10.004003","article-title":"Pilot study of transcranial photobiomodulation of lymphatic clearance of beta-amyloid from the mouse brain: Breakthrough strategies for non-pharmacologic therapy of Alzheimer's disease","volume":"10","author":"Zinchenko","year":"2019","journal-title":"BioMed Opt Express"},{"key":"B86","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.3390\/microorganisms13122659","article-title":"Gut microbiota-targeted photobiomodulation ameliorates Alzheimer's pathology via the gut-brain axis: Comparable efficacy to transcranial irradiation","volume":"13","author":"Cao","year":"2025","journal-title":"Microorganisms"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-021-01069-4","article-title":"Improved spatial memory and neuroinflammatory profile changes in aged rats submitted to photobiomodulation therapy","volume":"42","author":"Cardoso","year":"2022","journal-title":"Cell Mol Neurobiol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3233\/jad-210058","article-title":"Pilot study on dose-dependent effects of transcranial photobiomodulation on brain electrical oscillations: A potential therapeutic target in Alzheimer's disease","volume":"83","author":"Spera","year":"2021","journal-title":"J Alzheimers Dis"},{"key":"B89","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.3390\/nano14131093","article-title":"Raman spectroscopy reveals photobiomodulation-induced \u03b1-helix to \u03b2-sheet transition in tubulins: Potential implications for Alzheimer's and other neurodegenerative diseases","volume":"14","author":"Di Gregorio","year":"2024","journal-title":"Nanomaterials (Basel)"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2024.02.012","article-title":"Transcranial photobiomodulation increases intrinsic brain activity within irradiated areas in early Alzheimer's disease: Potential link with cerebral metabolism","volume":"17","author":"Gaggi","year":"2024","journal-title":"Brain Stimul"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1177\/13872877251361033","article-title":"Improved cognitive function, efficiency, saccadic eye movement, and depressive symptoms in mild cognitive impairment with transcranial photobiomodulation","volume":"107","author":"Lee","year":"2025","journal-title":"J Alzheimers Dis"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2025.121305","article-title":"Transcranial photobiomodulation improves functional brain networks and working memory in healthy older adults: An fnirs study","volume":"316","author":"Yang","year":"2025","journal-title":"Neuroimage"},{"key":"B93","doi-asserted-by":"publisher","first-page":"066013","DOI":"10.1088\/1741-2552\/ac9ede","article-title":"Neuromodulation of brain power topography and network topology by prefrontal transcranial photobiomodulation","volume":"19","author":"Shahdadian","year":"2022","journal-title":"J Neural Eng"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.06.067","article-title":"Noninvasive ultrasonic induction of cerebrospinal fluid flow enhances intrathecal drug delivery","volume":"349","author":"Aryal","year":"2022","journal-title":"J Control Release"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70451","article-title":"Restoration of glymphatic influx after photothrombotic stroke using low-intensity focused ultrasound","volume":"31","author":"Hsiao","year":"2025","journal-title":"CNS Neurosci Ther"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002175","article-title":"Ultrasound enhanced delivery of molecular imaging and therapeutic agents in Alzheimer's disease mouse models","volume":"3","author":"Raymond","year":"2008","journal-title":"PloS One"},{"key":"B97","doi-asserted-by":"publisher","first-page":"75","DOI":"10.3390\/pharmaceutics17010075","article-title":"Single exposure to low-intensity focused ultrasound causes biphasic opening of the blood-brain barrier through secondary mechanisms","volume":"17","author":"Arsiwala","year":"2025","journal-title":"Pharmaceutics"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.07.026","article-title":"Ultrasound-mediated delivery of novel tau-specific monoclonal antibody enhances brain uptake but not therapeutic efficacy","volume":"349","author":"Bajracharya","year":"2022","journal-title":"J\u00a0Control Release"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2018.05.012","article-title":"Whole-brain low-intensity pulsed ultrasound therapy markedly improves cognitive dysfunctions in mouse models of dementia - crucial roles of endothelial nitric oxide synthase","volume":"11","author":"Eguchi","year":"2018","journal-title":"Brain Stimul"},{"key":"B100","doi-asserted-by":"publisher","first-page":"41257","DOI":"10.1038\/s41598-025-25122-0","article-title":"Feasibility of ultrasound-mediated blood-brain barrier opening in sheep using sonolucent cranial implants","volume":"15","author":"Song","year":"2025","journal-title":"Sci Rep"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.3171\/2022.9.Jns221565","article-title":"Focused ultrasound-mediated blood-brain barrier opening in Alzheimer's disease: Long-term safety, imaging, and cognitive outcomes","volume":"139","author":"Rezai","year":"2023","journal-title":"J Neurosurg"},{"key":"B102","doi-asserted-by":"publisher","first-page":"2120","DOI":"10.3390\/pharmaceutics14102120","article-title":"High incidence of intracerebral hemorrhaging associated with the application of low-intensity focused ultrasound following acute cerebrovascular injury by intracortical injection","volume":"14","author":"Kim","year":"2022","journal-title":"Pharmaceutics"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.7150\/thno.81951","article-title":"High-intensity interval training ameliorates Alzheimer's disease-like pathology by regulating astrocyte phenotype-associated Aqp4 polarization","volume":"13","author":"Feng","year":"2023","journal-title":"Theranostics"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2025.111263","article-title":"Aerobic exercise improves clearance of amyloid-\u03b2 via the glymphatic system in a mouse model of Alzheimer's disease","volume":"222","author":"Liang","year":"2025","journal-title":"Brain Res Bull"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00144","article-title":"Voluntary exercise promotes glymphatic clearance of amyloid beta and reduces the activation of astrocytes and microglia in aged mice","volume":"10","author":"He","year":"2017","journal-title":"Front Mol Neurosci"},{"key":"B106","doi-asserted-by":"publisher","first-page":"3360","DOI":"10.1038\/s41467-025-58726-1","article-title":"Long-term physical exercise facilitates putative glymphatic and meningeal lymphatic vessel flow in humans","volume":"16","author":"Yoo","year":"2025","journal-title":"Nat Commun"},{"key":"B107","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s40035-025-00497-2","article-title":"Long-term exercise enhances meningeal lymphatic vessel plasticity and drainage in a mouse model of Alzheimer's disease","volume":"14","author":"Chen","year":"2025","journal-title":"Transl Neurodegener"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.335169","article-title":"Aquaporin 4 deficiency eliminates the beneficial effects of voluntary exercise in a mouse model of Alzheimer's disease","volume":"17","author":"Liu","year":"2022","journal-title":"Neural Regener Res"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2024.114770","article-title":"Voluntary wheel exercise improves glymphatic clearance and ameliorates colitis-associated cognitive impairment in aged mice by inhibiting Trpv4-induced astrocytic calcium activity","volume":"376","author":"Li","year":"2024","journal-title":"Exp Neurol"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aav5447","article-title":"Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia","volume":"5","author":"Hablitz","year":"2019","journal-title":"Sci Adv"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000213955","article-title":"Continuous positive airway pressure and progression of enlarged perivascular spaces in adults with obstructive sleep apnea","volume":"105","author":"Sommer","year":"2025","journal-title":"Neurology"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202411-2221OC","article-title":"Impact of sleep apnea on perivascular diffusivity and cognition: A 4-year prospective cohort study","volume":"211","author":"Lee","year":"2025","journal-title":"Am J Respir Crit Care Med"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-022-11530-z","article-title":"Impaired glymphatic drainage underlying obstructive sleep apnea is associated with cognitive dysfunction","volume":"270","author":"Wang","year":"2023","journal-title":"J Neurol"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2026.107325","article-title":"Increased MRI-derived parenchymal cerebral spinal fluid mapping in untreated obstructive sleep apnea patients","volume":"221","author":"Keil","year":"2026","journal-title":"Neurobiol Dis"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.232274","article-title":"Association of MRI indexes of the perivascular space network and cognitive impairment in patients with obstructive sleep apnea","volume":"311","author":"Lin","year":"2024","journal-title":"Radiology"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.170270","article-title":"Continuous positive airway pressure increases CSF flow and glymphatic transport","volume":"8","author":"Ozturk","year":"2023","journal-title":"JCI Insight"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3889","article-title":"Association between slow-wave sleep loss and incident dementia","volume":"80","author":"Himali","year":"2023","journal-title":"JAMA Neurol"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae245","article-title":"Brain metabolites are associated with sleep architecture and cognitive functioning in older adults","volume":"6","author":"Mueller","year":"2024","journal-title":"Brain Commun"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.70292","article-title":"Overnight dynamics of ventricular cerebrospinal fluid amyloid-beta, lactate and hypocretin in patients with hydrocephalus: A pilot study","volume":"35","author":"Riedel","year":"2026","journal-title":"J Sleep Res"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.28759","article-title":"Current understanding of the anatomy, physiology, and magnetic resonance imaging of neurofluids: Update from the 2022 \"ISMRM Imaging Neurofluids Study Group\" workshop in Rome","volume":"59","author":"Agarwal","year":"2024","journal-title":"J Magn Reson Imaging"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.3348\/kjr.2020.0042","article-title":"Neurofluid dynamics and the glymphatic system: A neuroimaging perspective","volume":"21","author":"Taoka","year":"2020","journal-title":"Korean J Radiol"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.28977","article-title":"Noninvasive magnetic resonance imaging measures of glymphatic system activity","volume":"59","author":"Kamagata","year":"2024","journal-title":"J\u00a0Magn Reson Imaging"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-0312-z","article-title":"Perivascular spaces in the brain: Anatomy, physiology and pathology","volume":"16","author":"Wardlaw","year":"2020","journal-title":"Nat Rev Neurol"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax5440","article-title":"Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep","volume":"366","author":"Fultz","year":"2019","journal-title":"Science"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-018-0021-x","article-title":"Noninvasive 40-Hz light flicker to recruit microglia and reduce amyloid beta load","volume":"13","author":"Singer","year":"2018","journal-title":"Nat Protoc"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1016\/j.pdpdt.2020.101777","article-title":"Nutritional ketosis and photobiomodulation remediate mitochondria warding off Alzheimer's disease in a diabetic, ApoE4+ patient with mild cognitive impairment: A case report","volume":"30","author":"Horner","year":"2020","journal-title":"Photodiagnosis Photodyn Ther"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.70051","article-title":"CSF proteomics reveals changes in myelin and synaptic biology after Spectris treatment","volume":"11","author":"Haj\u00f3s","year":"2025","journal-title":"Alzheimers Dement (N Y)"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123905","article-title":"Piezoelectric nanoparticle-driven rhythmic ultrasound neuromodulation for treatment of early-stage Alzheimer's disease","volume":"328","author":"Li","year":"2026","journal-title":"Biomaterials"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1177\/13872877251333614","article-title":"Repeated neuromodulation with low-intensity focused ultrasound in patients with Alzheimer's disease","volume":"105","author":"Jeong","year":"2025","journal-title":"J Alzheimers Dis"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2002571117","article-title":"Noninvasive hippocampal blood-brain barrier opening in Alzheimer's disease with focused ultrasound","volume":"117","author":"Rezai","year":"2020","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1884893\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T10:54:09Z","timestamp":1790160849000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1884893\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":130,"alternative-id":["10.3389\/fimmu.2026.1884893"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1884893","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]},"article-number":"1884893"}}