{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:17:30Z","timestamp":1793319450838,"version":"4.5.0"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460264"],"award-info":[{"award-number":["82460264"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the leading type of dementia globally, characterized by a complex pathogenesis that involves various comorbidities. An imbalance in the production and clearance of amyloid \u03b2-protein (A\u03b2) peptides in the brain is a key pathological mechanism of AD, with the glymphatic system playing a crucial role in A\u03b2 clearance. Comorbidities associated with AD, such as diabetes, depression, and hypertension, not only affect A\u03b2 production but also impair the brain\u2019s lymphatic system. Abnormalities in the structure and function of this system further weaken A\u03b2 clearance capabilities, and the presence of comorbidities may exacerbate this process. This paper aims to review the role and specific mechanisms of impaired A\u03b2 clearance via the glymphatic system in the context of AD comorbidities, providing new insights for the prevention and treatment of AD. Overall, the damage to the glymphatic system primarily focuses on aquaporin-4 (AQP4) and perivascular spaces (PVS), suggesting that maintaining the health of the glymphatic system may help slow the progression of AD and its comorbidities. Additionally, given the ongoing controversies regarding the structure of the glymphatic system, this paper revisits this structure and discusses the principles and characteristics of current detection methods for the glymphatic system.<\/jats:p>","DOI":"10.3389\/fneur.2024.1474439","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T10:53:27Z","timestamp":1732532007000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["The role and mechanism of A\u03b2 clearance dysfunction in the glymphatic system in Alzheimer\u2019s disease comorbidity"],"prefix":"10.3389","volume":"15","author":[{"given":"Hailang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/s41398-022-02268-3","article-title":"Association between multimorbidity status and incident dementia: a prospective cohort study of 245,483 participants","volume":"12","author":"Hu","year":"2022","journal-title":"Transl Psychiatry"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1002\/alz.13519","article-title":"Multimorbidity, cognitive phenotypes, and Alzheimer\u2019s disease plasma biomarkers in older adults: a population-based study","volume":"20","author":"Ren","year":"2024","journal-title":"Alzheimers Dement"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"773","DOI":"10.3233\/JAD-170786","article-title":"Medical comorbidity in Alzheimer\u2019s disease: a nested case-control study","volume":"63","author":"Wang","year":"2018","journal-title":"J Alzheimers Dis"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"104987","DOI":"10.1016\/j.isci.2022.104987","article-title":"The glymphatic system: current understanding and modeling","volume":"25","author":"Bohr","year":"2022","journal-title":"iScience"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"147ra111","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":"ref7","doi-asserted-by":"publisher","first-page":"7698","DOI":"10.1523\/JNEUROSCI.0619-21.2021","article-title":"The glymphatic system: a novel component of fundamental neurobiology","volume":"41","author":"Hablitz","year":"2021","journal-title":"J Neurosci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1093\/brain\/awae065","article-title":"Macroscopic changes in aquaporin-4 underlie blast traumatic brain injury-related impairment in glymphatic function","volume":"147","author":"Braun","year":"2024","journal-title":"Brain"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12987-024-00527-7","article-title":"Role of aquaporin-4 polarization in extracellular solute clearance","volume":"21","author":"Bojarskaite","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"90","DOI":"10.3390\/cells8020090","article-title":"Aquaporin-4 water channel in the brain and its implication for health and disease","volume":"8","author":"Mader","year":"2019","journal-title":"Cells"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"137","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":"ref12","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1111\/jon.12493","article-title":"Neuroimaging of dilated perivascular spaces: from benign and pathologic causes to mimics","volume":"28","author":"Rudie","year":"2018","journal-title":"J Neuroimaging"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/S1474-4422(13)70124-8","article-title":"Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration","volume":"12","author":"Wardlaw","year":"2013","journal-title":"Lancet Neurol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"2","DOI":"10.5853\/jos.2015.17.1.2","article-title":"Lacunar infarction and small vessel disease: pathology and pathophysiology","volume":"17","author":"Caplan","year":"2015","journal-title":"J Stroke"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"862","DOI":"10.3174\/ajnr.A5129","article-title":"Brain perivascular spaces as biomarkers of vascular risk: results from the northern Manhattan study","volume":"38","author":"Gutierrez","year":"2017","journal-title":"AJNR Am J Neuroradiol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1161\/01.ATV.0000160548.78317.29","article-title":"Mechanisms, pathophysiology, and therapy of arterial stiffness","volume":"25","author":"Zieman","year":"2005","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.1007\/s00018-020-03706-5","article-title":"Cerebrospinal fluid outflow: a review of the historical and contemporary evidence for arachnoid villi, perineural routes, and dural lymphatics","volume":"78","author":"Proulx","year":"2021","journal-title":"Cell Mol Life Sci"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1126\/science.adp1705","article-title":"The anatomy of brainwashing","volume":"385","author":"Kipnis","year":"2024","journal-title":"Science"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"689098","DOI":"10.3389\/fnagi.2021.689098","article-title":"The glymphatic system: a novel therapeutic target for stroke treatment","volume":"13","author":"Lv","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.medcli.2020.08.020","article-title":"The glymphatic system and its involvement in disorders of the nervous system","volume":"156","author":"Toriello","year":"2021","journal-title":"Med Clin"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"385","DOI":"10.47626\/1516-4446-2023-0049","article-title":"Glymphatic system waste clearance and Alzheimer\u2019s disease","volume":"45","author":"Barichello de Quevedo","year":"2023","journal-title":"Braz J Psychiatry"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1177\/0271678X17737984","article-title":"Paravascular spaces at the brain surface: low resistance pathways for cerebrospinal fluid flow","volume":"38","author":"Bedussi","year":"2018","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1199","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":"ref24","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/s41586-024-07108-6","article-title":"Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance","volume":"627","author":"Jiang-Xie","year":"2024","journal-title":"Nature"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1177\/0271678X15622047","article-title":"Ultra-fast magnetic resonance encephalography of physiological brain activity\u2014glymphatic pulsation mechanisms?","volume":"36","author":"Kiviniemi","year":"2016","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.1007\/s11064-015-1581-6","article-title":"The glymphatic system: a beginner\u2019s guide","volume":"40","author":"Jessen","year":"2015","journal-title":"Neurochem Res"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1523\/JNEUROSCI.3246-14.2015","article-title":"Inspiration is the major regulator of human CSF flow","volume":"35","author":"Dreha-Kulaczewski","year":"2015","journal-title":"J Neurosci"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s41586-019-1419-5","article-title":"Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid","volume":"572","author":"Ahn","year":"2019","journal-title":"Nature"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1007\/s00330-023-10122-3","article-title":"Glymphatic system impairment in Alzheimer\u2019s disease: associations with perivascular space volume and cognitive function","volume":"34","author":"Zhang","year":"2024","journal-title":"Eur Radiol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"295","DOI":"10.3233\/JAD-220534","article-title":"Relationships between the deposition of amyloid-\u03b2 and tau protein and glymphatic system activity in Alzheimer\u2019s disease: diffusion tensor image study","volume":"90","author":"Ota","year":"2022","journal-title":"J Alzheimers Dis"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1007\/s11604-017-0617-z","article-title":"Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer\u2019s disease cases","volume":"35","author":"Taoka","year":"2017","journal-title":"Jpn J Radiol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.trci.2017.05.001","article-title":"The effects of noncoding aquaporin-4 single-nucleotide polymorphisms on cognition and functional progression of Alzheimer\u2019s disease","volume":"3","author":"Burfeind","year":"2017","journal-title":"Alzheimers Dement"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"106100","DOI":"10.1016\/j.nbd.2023.106100","article-title":"The effect of aquaporin-4 mis-localization on A\u03b2 deposition in mice","volume":"181","author":"Pedersen","year":"2023","journal-title":"Neurobiol Dis"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.4103\/1673-5374.335169","article-title":"Aquaporin 4 deficiency eliminates the beneficial effects of voluntary exercise in a mouse model of Alzheimer\u2019s disease","volume":"17","author":"Liu","year":"2022","journal-title":"Neural Regen Res"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"176","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":"ref36","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1126\/science.1241224","article-title":"Sleep drives metabolite clearance from the adult brain","volume":"342","author":"Xie","year":"2013","journal-title":"Science"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"zsy025","DOI":"10.1093\/sleep\/zsy025","article-title":"Sleep deprivation and cerebrospinal fluid biomarkers for Alzheimer\u2019s disease","volume":"41","author":"Olsson","year":"2018","journal-title":"Sleep"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"11034","DOI":"10.1523\/JNEUROSCI.1625-15.2015","article-title":"The effect of body posture on brain glymphatic transport","volume":"35","author":"Lee","year":"2015","journal-title":"J Neurosci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s00018-023-04736-5","article-title":"Brain washing and neural health: role of age, sleep, and the cerebrospinal fluid melatonin rhythm","volume":"80","author":"Reiter","year":"2023","journal-title":"Cell Mol Life Sci"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/s41398-023-02614-z","article-title":"Melatonin alleviates depression-like behaviors and cognitive dysfunction in mice by regulating the circadian rhythm of AQP4 polarization","volume":"13","author":"Yao","year":"2023","journal-title":"Transl Psychiatry"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"110887","DOI":"10.1016\/j.biopha.2020.110887","article-title":"Melatonin regulates A\u03b2 production\/clearance balance and A\u03b2 neurotoxicity: a potential therapeutic molecule for Alzheimer\u2019s disease","volume":"132","author":"Li","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"3221","DOI":"10.3390\/ijms24043221","article-title":"Brain waste removal system and sleep: photobiomodulation as an innovative strategy for night therapy of brain diseases","volume":"24","author":"Semyachkina-Glushkovskaya","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e13028","DOI":"10.1111\/bpa.13028","article-title":"Chronic sleep deprivation altered the expression of circadian clock genes and aggravated Alzheimer\u2019s disease neuropathology","volume":"32","author":"Niu","year":"2022","journal-title":"Brain Pathol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1186\/s12974-023-02944-1","article-title":"Repeated sleep deprivation decreases the flux into hexosamine biosynthetic pathway\/O-GlcNAc cycling and aggravates Alzheimer\u2019s disease neuropathology in adult zebrafish","volume":"20","author":"Park","year":"2023","journal-title":"J Neuroinflammation"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.biopsych.2017.11.031","article-title":"The emerging relationship between interstitial fluid-cerebrospinal fluid exchange, amyloid-\u03b2, and sleep","volume":"83","author":"Boespflug","year":"2018","journal-title":"Biol Psychiatry"},{"key":"ref46","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":"ref47","doi-asserted-by":"publisher","first-page":"5446","DOI":"10.1007\/s00330-022-08649-y","article-title":"MRI-visible enlarged perivascular spaces: imaging marker to predict cognitive impairment in older chronic insomnia patients","volume":"32","author":"Wang","year":"2022","journal-title":"Eur Radiol"},{"key":"ref48","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":"ref49","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02778-0","article-title":"Effects of sleep on the glymphatic functioning and multimodal human brain network affecting memory in older adults","author":"Ma","year":"2024","journal-title":"Mol Psychiatry"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1038\/s41467-023-36643-5","article-title":"Sleep cycle-dependent vascular dynamics in male mice and the predicted effects on perivascular cerebrospinal fluid flow and solute transport","volume":"14","author":"Bojarskaite","year":"2023","journal-title":"Nat Commun"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02691-6","article-title":"Melatonin: a potential nighttime guardian against Alzheimer\u2019s","author":"Zhang","year":"2024","journal-title":"Mol Psychiatry"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/s41572-022-00376-4","article-title":"Multimorbidity","volume":"8","author":"Skou","year":"2022","journal-title":"Nat Rev Dis Primers"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.1093\/gerona\/glz185","article-title":"Prevalence and patterns of multimorbidity in a nationally representative sample of older Chinese: results from the China health and retirement longitudinal study","volume":"75","author":"Yao","year":"2020","journal-title":"J Gerontol A"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1136\/jnnp-2014-310095","article-title":"Risk factors for predicting progression from mild cognitive impairment to Alzheimer\u2019s disease: a systematic review and meta-analysis of cohort studies","volume":"87","author":"Li","year":"2016","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"401","DOI":"10.3390\/biomedicines12020401","article-title":"The glymphatic response to the development of type 2 diabetes","volume":"12","author":"Boyd","year":"2024","journal-title":"Biomedicines"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1177\/0271678X16654702","article-title":"Impairment of the glymphatic system after diabetes","volume":"37","author":"Jiang","year":"2017","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"2817","DOI":"10.1016\/j.apsb.2023.03.018","article-title":"Peripheral origin exosomal microRNAs aggravate glymphatic system dysfunction in diabetic cognitive impairment","volume":"13","author":"Zhang","year":"2023","journal-title":"Acta Pharm Sin B"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1017\/S1041610217002368","article-title":"Depressive and anxiety symptoms and cortical amyloid deposition among cognitively normal elderly persons: the Mayo Clinic Study of Aging","volume":"30","author":"Krell-Roesch","year":"2018","journal-title":"Int Psychogeriatr"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"e32598","DOI":"10.1002\/brb3.2598","article-title":"Perivascular spaces as a marker of psychological trauma in depression: a 7-Tesla MRI study","volume":"12","author":"Ranti","year":"2022","journal-title":"Brain Behav"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s00213-016-4473-9","article-title":"Mechanism of depression as a risk factor in the development of Alzheimer's disease: the function of AQP4 and the glymphatic system","volume":"234","author":"Xia","year":"2017","journal-title":"Psychopharmacology"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3934\/Neuroscience.2021005","article-title":"The biological pathways of Alzheimer disease: a review","volume":"8","author":"Calabr\u00f2","year":"2021","journal-title":"AIMS Neurosci"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"883503","DOI":"10.3389\/fnagi.2022.883503","article-title":"Mesenchymal stem cells improve cognitive impairment and reduce A\u03b2 deposition via promoting AQP4 polarity and relieving neuroinflammation in rats with chronic hypertension-induced cerebral small-vessel disease","volume":"14","author":"Liu","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"748","DOI":"10.3390\/biom12060748","article-title":"The underlying role of the glymphatic system and meningeal lymphatic vessels in cerebral small vessel disease","volume":"12","author":"Tian","year":"2022","journal-title":"Biomol Ther"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1136\/svn-2022-002191","article-title":"Impaired glymphatic system as evidenced by low diffusivity along perivascular spaces is associated with cerebral small vessel disease: a population-based study","volume":"8","author":"Tian","year":"2023","journal-title":"Stroke Vasc Neurol"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"fcad349","DOI":"10.1093\/braincomms\/fcad349","article-title":"Impaired cerebral interstitial fluid dynamics in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy","volume":"6","author":"Hsu","year":"2024","journal-title":"Brain Commun"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/s41581-021-00430-6","article-title":"Hypertension-induced cognitive impairment: from pathophysiology to public health","volume":"17","author":"Ungvari","year":"2021","journal-title":"Nat Rev Nephrol"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1001\/jamaneurol.2013.1342","article-title":"Risk factors for \u03b2-amyloid deposition in healthy aging: vascular and genetic effects","volume":"70","author":"Rodrigue","year":"2013","journal-title":"JAMA Neurol"},{"key":"ref68","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":"ref69","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.brainresbull.2020.04.008","article-title":"Concomitant enlargement of perivascular spaces and decrease in glymphatic transport in an animal model of cerebral small vessel disease","volume":"161","author":"Xue","year":"2020","journal-title":"Brain Res Bull"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"48","DOI":"10.3174\/ajnr.A7334","article-title":"An investigation of water diffusivity changes along the perivascular space in elderly subjects with hypertension","volume":"43","author":"Kikuta","year":"2022","journal-title":"AJNR Am J Neuroradiol"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1111\/bpa.12384","article-title":"Common impact of chronic kidney disease and brain microhemorrhages on cerebral A\u03b2 pathology in SHRSP","volume":"27","author":"Pirici","year":"2017","journal-title":"Brain Pathol"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"976089","DOI":"10.3389\/fneur.2022.976089","article-title":"Glymphatic system dysfunction in patients with early chronic kidney disease","volume":"13","author":"Heo","year":"2022","journal-title":"Front Neurol"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1159\/000530635","article-title":"Cognitive impairment in chronic kidney disease is associated with glymphatic system dysfunction","volume":"9","author":"Xu","year":"2023","journal-title":"Kidney Dis"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1093\/brain\/awab268","article-title":"The role of mTORC1 activation in seizure-induced exacerbation of Alzheimer's disease","volume":"145","author":"Gourmaud","year":"2022","journal-title":"Brain"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"1221775","DOI":"10.3389\/fneur.2023.1221775","article-title":"Localized proteomic differences in the choroid plexus of Alzheimer\u2019s disease and epilepsy patients","volume":"14","author":"Leitner","year":"2023","journal-title":"Front Neurol"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s00401-024-02683-4","article-title":"Similar brain proteomic signatures in Alzheimer\u2019s disease and epilepsy","volume":"147","author":"Leitner","year":"2024","journal-title":"Acta Neuropathol"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"e16097","DOI":"10.1111\/ene.16097","article-title":"Anti-seizure medication response and the glymphatic system in patients with focal epilepsy","volume":"31","author":"Kim","year":"2024","journal-title":"Eur J Neurol"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1002\/epi4.12594","article-title":"Glymphatic system dysfunction in temporal lobe epilepsy patients with hippocampal sclerosis","volume":"7","author":"Lee","year":"2022","journal-title":"Epilepsia Open"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"e2504","DOI":"10.1002\/brb3.2504","article-title":"Glymphatic system function in patients with newly diagnosed focal epilepsy","volume":"12","author":"Lee","year":"2022","journal-title":"Brain Behav"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"106322","DOI":"10.1016\/j.nbd.2023.106322","article-title":"Age- and glaucoma-induced changes to the ocular glymphatic system","volume":"188","author":"Wang","year":"2023","journal-title":"Neurobiol Dis"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"2905","DOI":"10.1038\/s41433-020-01219-w","article-title":"Do normal-tension and high-tension glaucoma result from brain and ocular glymphatic system disturbances, respectively?","volume":"35","author":"Wostyn","year":"2021","journal-title":"Eye"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.molmed.2019.11.008","article-title":"Glymphatic system impairment in Alzheimer\u2019s disease and idiopathic normal pressure hydrocephalus","volume":"26","author":"Reeves","year":"2020","journal-title":"Trends Mol Med"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1093\/brain\/awx191","article-title":"Glymphatic MRI in idiopathic normal pressure hydrocephalus","volume":"140","author":"Ringstad","year":"2017","journal-title":"Brain"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"3251","DOI":"10.1002\/alz.13789","article-title":"Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer\u2019s disease","volume":"20","author":"Huang","year":"2024","journal-title":"Alzheimers Dement"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"494e","DOI":"10.1097\/PRS.0000000000010933","article-title":"Rewiring the brain: the next frontier in supermicrosurgery","volume":"153","author":"Xie","year":"2024","journal-title":"Plast Reconstr Surg"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1038\/s43587-024-00691-3","article-title":"Restoration of cervical lymphatic vessel function in aging rescues cerebrospinal fluid drainage","volume":"4","author":"Du","year":"2024","journal-title":"Nat Aging"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"845","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":"ref88","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1126\/science.1197623","article-title":"Decreased clearance of CNS beta-amyloid in Alzheimer\u2019s disease","volume":"330","author":"Mawuenyega","year":"2010","journal-title":"Science"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"1383780","DOI":"10.3389\/fnins.2024.1383780","article-title":"DTI-ALPS index decreased in patients with type 2 diabetes mellitus","volume":"18","author":"Yu","year":"2024","journal-title":"Front Neurosci"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"20220315","DOI":"10.1259\/bjr.20220315","article-title":"Evaluation of glymphatic system activity by diffusion tensor image analysis along the perivascular space (DTI-ALPS) in dementia patients","volume":"96","author":"Liang","year":"2023","journal-title":"Br J Radiol"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.tins.2020.04.003","article-title":"The brain's glymphatic system: current controversies","volume":"43","author":"Mestre","year":"2020","journal-title":"Trends Neurosci"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s00234-023-03270-2","article-title":"Glymphatic imaging: a critical look at the DTI-ALPS index","volume":"66","author":"Ringstad","year":"2024","journal-title":"Neuroradiology"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nrneurol.2015.119","article-title":"Clearance systems in the brain-implications for Alzheimer disease","volume":"11","author":"Tarasoff-Conway","year":"2015","journal-title":"Nat Rev Neurol"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"7998","DOI":"10.1038\/s41467-024-52396-1","article-title":"Clearance and transport of amyloid \u03b2 by peripheral monocytes correlate with Alzheimer\u2019s disease progression","volume":"15","author":"Huang","year":"2024","journal-title":"Nat Commun"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/s44161-024-00445-9","article-title":"Sustained meningeal lymphatic vessel atrophy or expansion does not alter Alzheimer\u2019s disease-related amyloid pathology","volume":"3","author":"Antila","year":"2024","journal-title":"Nat Cardiovasc Res"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41586-021-03489-0","article-title":"Meningeal lymphatics affect microglia responses and anti-A\u03b2 immunotherapy","volume":"593","author":"Da Mesquita","year":"2021","journal-title":"Nature"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.bbi.2020.07.022","article-title":"Polyunsaturated fatty acid supplement alleviates depression-incident cognitive dysfunction by protecting the cerebrovascular and glymphatic systems","volume":"89","author":"Liu","year":"2020","journal-title":"Brain Behav Immun"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"1908","DOI":"10.1002\/jnr.25104","article-title":"Plasticity of the spinal glymphatic system in male SD rats with painful diabetic neuropathy induced by type 2 diabetes mellitus","volume":"100","author":"Wang","year":"2022","journal-title":"J Neurosci Res"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/s40478-023-01606-w","article-title":"Reduction of oxytocin-containing neurons and enhanced glymphatic activity in the hypothalamic paraventricular nucleus of patients with type 2 diabetes mellitus","volume":"11","author":"Correa-da-Silva","year":"2023","journal-title":"Acta Neuropathol Commun"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"87","DOI":"10.12779\/dnd.2023.22.3.87","article-title":"Association of type 2 diabetes mellitus with perivascular spaces and cerebral amyloid angiopathy in Alzheimer\u2019s disease: insights from MRI imaging","volume":"22","author":"Munis","year":"2023","journal-title":"Dement Neurocogn Disord"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"1362457","DOI":"10.3389\/fnagi.2024.1362457","article-title":"Assessing interstitial fluid dynamics in type 2 diabetes mellitus and prediabetes cases through diffusion tensor imaging analysis along the perivascular space","volume":"16","author":"Tuerxun","year":"2024","journal-title":"Front Aging Neurosci"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1007\/s12264-020-00539-x","article-title":"Iron aggravates the depressive phenotype of stressed mice by compromising the glymphatic system","volume":"36","author":"Liang","year":"2020","journal-title":"Neurosci Bull"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"118257","DOI":"10.1016\/j.neuroimage.2021.118257","article-title":"Glymphatic clearance function in patients with cerebral small vessel disease","volume":"238","author":"Zhang","year":"2021","journal-title":"NeuroImage"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"6096","DOI":"10.1007\/s00330-023-09796-6","article-title":"Evaluation of glymphatic-meningeal lymphatic system with intravenous gadolinium-based contrast-enhancement in cerebral small-vessel disease","volume":"33","author":"Zhang","year":"2023","journal-title":"Eur Radiol"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"2895","DOI":"10.1111\/ene.15450","article-title":"Glymphatic dysfunction correlates with severity of small vessel disease and cognitive impairment in cerebral amyloid angiopathy","volume":"29","author":"Xu","year":"2022","journal-title":"Eur J Neurol"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"6365","DOI":"10.1523\/JNEUROSCI.1974-18.2019","article-title":"Impaired glymphatic transport in spontaneously hypertensive rats","volume":"39","author":"Mortensen","year":"2019","journal-title":"J Neurosci"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1161\/STROKEAHA.118.020163","article-title":"Arterial stiffness is associated with basal ganglia enlarged perivascular spaces and cerebral small vessel disease load","volume":"49","author":"Riba-Llena","year":"2018","journal-title":"Stroke"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"2265665","DOI":"10.1080\/0886022X.2023.2265665","article-title":"Changes in the glymphatic system before and after dialysis initiation in patients with end-stage kidney disease","volume":"45","author":"Lee","year":"2023","journal-title":"Ren Fail"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.seizure.2024.06.021","article-title":"Associations of glymphatic function with structural network and cognition in self-limited epilepsy with centrotemporal spikes","volume":"120","author":"Gao","year":"2024","journal-title":"Seizure"},{"key":"ref110","doi-asserted-by":"publisher","first-page":"eaaw3210","DOI":"10.1126\/scitranslmed.aaw3210","article-title":"An ocular glymphatic clearance system removes \u03b2-amyloid from the rodent eye","volume":"12","author":"Wang","year":"2020","journal-title":"Sci Transl Med"},{"key":"ref111","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1002\/glia.23528","article-title":"Loss of perivascular aquaporin-4 in idiopathic normal pressure hydrocephalus","volume":"67","author":"Hasan-Olive","year":"2019","journal-title":"Glia"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"108123","DOI":"10.1016\/j.clineuro.2024.108123","article-title":"Patients with normal pressure hydrocephalus have fewer enlarged perivascular spaces in the centrum semiovale compared to cognitively unimpaired individuals","volume":"237","author":"Switzer","year":"2024","journal-title":"Clin Neurol Neurosurg"}],"updated-by":[{"DOI":"10.3389\/fneur.2025.1633297","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000}}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1474439\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T14:53:14Z","timestamp":1749221594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1474439\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,25]]},"references-count":112,"alternative-id":["10.3389\/fneur.2024.1474439"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2024.1474439","relation":{"corrigendum":[{"id-type":"doi","id":"10.3389\/fneur.2025.1633297","asserted-by":"object"}]},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,25]]},"article-number":"1474439"}}