{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:29:17Z","timestamp":1786350557081,"version":"build-2736575974"},"reference-count":128,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Innovation of Science and Technology 2030 \u2013 Major Project on Brain Science and Brain-Inspired Intelligence Research","award":["2021ZD0201802"],"award-info":[{"award-number":["2021ZD0201802"]}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["82471450"],"award-info":[{"award-number":["82471450"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Xicheng District Science and Technology Special Project","award":["XCSTS-SD2024-02"],"award-info":[{"award-number":["XCSTS-SD2024-02"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1007\/s00415-026-13997-6","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T09:42:36Z","timestamp":1784713356000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serial failure of the brain clearance continuum in Alzheimer\u2019s disease: mechanisms and therapeutic perspectives"],"prefix":"10.1007","volume":"273","author":[{"given":"Qi","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidi","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heya","family":"Luan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boye","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuqiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyuan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7380-7451","authenticated-orcid":false,"given":"Cuibai","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"13997_CR1","doi-asserted-by":"publisher","unstructured":"2024 Alzheimer\u2019s disease facts and figures 2024. Alzheimers Dement 20:3708-821.https:\/\/doi.org\/10.1002\/alz.13809","DOI":"10.1002\/alz.13809"},{"key":"13997_CR2","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1016\/s0140-6736(20)32205-4","volume":"397","author":"P Scheltens","year":"2021","unstructured":"Scheltens P, De Strooper B, Kivipelto M, Holstege H, Ch\u00e9telat G, Teunissen CE et al (2021) Alzheimer\u2019s disease. Lancet 397:1577\u20131590. https:\/\/doi.org\/10.1016\/s0140-6736(20)32205-4","journal-title":"Lancet"},{"key":"13997_CR3","doi-asserted-by":"publisher","first-page":"e1534","DOI":"10.1016\/s2214-109x(24)00264-x","volume":"12","author":"S Chen","year":"2024","unstructured":"Chen S, Cao Z, Nandi A, Counts N, Jiao L, Prettner K et al (2024) The global macroeconomic burden of Alzheimer\u2019s disease and other dementias: estimates and projections for 152 countries or territories. Lancet Glob Health 12:e1534\u2013e1543. https:\/\/doi.org\/10.1016\/s2214-109x(24)00264-x","journal-title":"Lancet Glob Health"},{"key":"13997_CR4","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","volume":"71","author":"GS Bloom","year":"2014","unstructured":"Bloom GS (2014) Amyloid-\u03b2 and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol 71:505\u2013508. https:\/\/doi.org\/10.1001\/jamaneurol.2013.5847","journal-title":"JAMA Neurol"},{"key":"13997_CR5","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15252\/emmm.201606210","volume":"8","author":"DJ Selkoe","year":"2016","unstructured":"Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer\u2019s disease at 25 years. EMBO Mol Med 8:595\u2013608. https:\/\/doi.org\/10.15252\/emmm.201606210","journal-title":"EMBO Mol Med"},{"key":"13997_CR6","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2212948","volume":"388","author":"CH van Dyck","year":"2023","unstructured":"van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M et al (2023) Lecanemab in early Alzheimer\u2019s disease. N Engl J Med 388:9\u201321. https:\/\/doi.org\/10.1056\/NEJMoa2212948","journal-title":"N Engl J Med"},{"key":"13997_CR7","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1126\/science.abb8739","volume":"370","author":"M Nedergaard","year":"2020","unstructured":"Nedergaard M, Goldman SA (2020) Glymphatic failure as a final common pathway to dementia. Sci 370:50\u201356. https:\/\/doi.org\/10.1126\/science.abb8739","journal-title":"Sci"},{"key":"13997_CR8","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.tins.2020.12.002","volume":"44","author":"M Segarra","year":"2021","unstructured":"Segarra M, Aburto MR, Acker-Palmer A (2021) Blood-brain barrier dynamics to maintain brain Homeostasis. Trends Neurosci 44:393\u2013405. https:\/\/doi.org\/10.1016\/j.tins.2020.12.002","journal-title":"Trends Neurosci"},{"key":"13997_CR9","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/s41392-025-02177-z","volume":"10","author":"Q Zhang","year":"2025","unstructured":"Zhang Q, Niu Y, Li Y, Xia C, Chen Z, Chen Y et al (2025) Meningeal lymphatic drainage: novel insights into central nervous system disease. Signal Transduct Target Ther 10:142. https:\/\/doi.org\/10.1038\/s41392-025-02177-z","journal-title":"Signal Transduct Target Ther"},{"key":"13997_CR10","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/s42003-022-03037-0","volume":"5","author":"DL Elbert","year":"2022","unstructured":"Elbert DL, Patterson BW, Lucey BP, Benzinger TLS, Bateman RJ (2022) Importance of CSF-based A\u03b2 clearance with age in humans increases with declining efficacy of blood\u2013brain barrier\/proteolytic pathways. Commun Biol 5:98. https:\/\/doi.org\/10.1038\/s42003-022-03037-0","journal-title":"Commun Biol"},{"key":"13997_CR11","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.1007\/s00018-020-03706-5","volume":"78","author":"ST Proulx","year":"2021","unstructured":"Proulx ST (2021) Cerebrospinal fluid outflow: a review of the historical and contemporary evidence for arachnoid villi, perineural routes, and dural lymphatics. Cell Mol Life Sci 78:2429\u20132457. https:\/\/doi.org\/10.1007\/s00018-020-03706-5","journal-title":"Cell Mol Life Sci"},{"key":"13997_CR12","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s12987-018-0113-6","volume":"15","author":"SB Hladky","year":"2018","unstructured":"Hladky SB, Barrand MA (2018) Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood\u2013brain barrier. Fluids Barriers CNS 15:30. https:\/\/doi.org\/10.1186\/s12987-018-0113-6","journal-title":"Fluids Barriers CNS"},{"key":"13997_CR13","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1172\/jci81108","volume":"126","author":"SE Storck","year":"2016","unstructured":"Storck SE, Meister S, Nahrath J, Mei\u00dfner JN, Schubert N, Di Spiezio A et al (2016) Endothelial LRP1 transports amyloid-\u03b2(1\u201342) across the blood\u2013brain barrier. J Clin Invest 126:123\u2013136. https:\/\/doi.org\/10.1172\/jci81108","journal-title":"J Clin Invest"},{"key":"13997_CR14","doi-asserted-by":"publisher","first-page":"147ra11","DOI":"10.1126\/scitranslmed.3003748","volume":"4","author":"JJ Iliff","year":"2012","unstructured":"Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA et al (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \u03b2. Sci Transl Med 4:147ra11. https:\/\/doi.org\/10.1126\/scitranslmed.3003748","journal-title":"Sci Transl Med"},{"key":"13997_CR15","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature14432","volume":"523","author":"A Louveau","year":"2015","unstructured":"Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nat 523:337\u2013341. https:\/\/doi.org\/10.1038\/nature14432","journal-title":"Nat"},{"key":"13997_CR16","doi-asserted-by":"publisher","first-page":"3153","DOI":"10.1016\/j.immuni.2025.11.010","volume":"58","author":"MW Kim","year":"2025","unstructured":"Kim MW, Kipnis J (2025) Glymphatics and meningeal lymphatics unlock the brain-immune code. Immun 58:3153. https:\/\/doi.org\/10.1016\/j.immuni.2025.11.010","journal-title":"Immun"},{"key":"13997_CR17","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1177\/0271678x221082786","volume":"42","author":"J Christensen","year":"2022","unstructured":"Christensen J, Li C, Mychasiuk R (2022) Choroid plexus function in neurological homeostasis and disorders: the awakening of the circadian clocks and orexins. J Cereb Blood Flow Metab 42:1163\u20131175. https:\/\/doi.org\/10.1177\/0271678x221082786","journal-title":"J Cereb Blood Flow Metab"},{"key":"13997_CR18","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s12974-022-02500-3","volume":"19","author":"Y Yang","year":"2022","unstructured":"Yang Y, He J, Wang Y, Wang C, Tan C, Liao J et al (2022) Targeting choroid plexus epithelium as a novel therapeutic strategy for hydrocephalus. J Neuroinflamm 19:156. https:\/\/doi.org\/10.1186\/s12974-022-02500-3","journal-title":"J Neuroinflamm"},{"key":"13997_CR19","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1084\/jem.20142290","volume":"212","author":"A Aspelund","year":"2015","unstructured":"Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M et al (2015) A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med 212:991\u2013999. https:\/\/doi.org\/10.1084\/jem.20142290","journal-title":"J Exp Med"},{"key":"13997_CR20","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s12987-020-00196-2","volume":"17","author":"P Sol\u00e1r","year":"2020","unstructured":"Sol\u00e1r P, Zamani A, Kub\u00ed\u010dkov\u00e1 L, Dubov\u00fd P, Joukal M (2020) Choroid plexus and the blood-cerebrospinal fluid barrier in disease. Fluids Barriers CNS 17:35. https:\/\/doi.org\/10.1186\/s12987-020-00196-2","journal-title":"Fluids Barriers CNS"},{"key":"13997_CR21","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1152\/physrev.00004.2013","volume":"93","author":"HH Damkier","year":"2013","unstructured":"Damkier HH, Brown PD, Praetorius J (2013) Cerebrospinal fluid secretion by the choroid plexus. Physiol Rev 93:1847\u20131892. https:\/\/doi.org\/10.1152\/physrev.00004.2013","journal-title":"Physiol Rev"},{"key":"13997_CR22","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s12974-024-03059-x","volume":"21","author":"R Sun","year":"2024","unstructured":"Sun R, Jiang H (2024) Border-associated macrophages in the central nervous system. J Neuroinflamm 21:67. https:\/\/doi.org\/10.1186\/s12974-024-03059-x","journal-title":"J Neuroinflamm"},{"key":"13997_CR23","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/s41586-022-05397-3","volume":"611","author":"A Drieu","year":"2022","unstructured":"Drieu A, Du S, Storck SE, Rustenhoven J, Papadopoulos Z, Dykstra T et al (2022) Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid. Nature 611:585\u2013593. https:\/\/doi.org\/10.1038\/s41586-022-05397-3","journal-title":"Nature"},{"key":"13997_CR24","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/s41467-020-20666-3","volume":"12","author":"H Xu","year":"2021","unstructured":"Xu H, Fame RM, Sadegh C, Sutin J, Naranjo C, Della S et al (2021) Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development. Nat Commun 12:447. https:\/\/doi.org\/10.1038\/s41467-020-20666-3","journal-title":"Nat Commun"},{"key":"13997_CR25","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1016\/j.neuron.2023.02.020","volume":"111","author":"C Sadegh","year":"2023","unstructured":"Sadegh C, Xu H, Sutin J, Fatou B, Gupta S, Pragana A et al (2023) Choroid plexus-targeted NKCC1 overexpression to treat post-hemorrhagic hydrocephalus. Neuron 111:1591\u2013608.e4. https:\/\/doi.org\/10.1016\/j.neuron.2023.02.020","journal-title":"Neuron"},{"key":"13997_CR26","doi-asserted-by":"publisher","DOI":"10.1177\/13872877261426578","author":"M Lv","year":"2026","unstructured":"Lv M, Wang Q, Yu G, Chen J, Zhou X, Chen Z et al (2026) Choroid plexus-glymphatic axis disruption in Alzheimer\u2019s disease: cerebrospinal fluid expansion as a mediator of metabolic dysfunction and cognitive decline. J Alzheimers Dis. https:\/\/doi.org\/10.1177\/13872877261426578","journal-title":"J Alzheimers Dis"},{"key":"13997_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-15923-8","volume":"15","author":"W Lin","year":"2025","unstructured":"Lin W, Chen H, Zhang Z, Zhang Y, Wang X, Guo Y et al (2025) Multimodal MRI reveals impaired glymphatic function with choroid plexus enlargement and cerebrospinal fluid expansion in Alzheimer\u2019s disease. Sci Rep 15:30409. https:\/\/doi.org\/10.1038\/s41598-025-15923-8","journal-title":"Sci Rep"},{"key":"13997_CR28","doi-asserted-by":"publisher","first-page":"e213953","DOI":"10.1212\/wnl.0000000000213953","volume":"105","author":"M Lin","year":"2025","unstructured":"Lin M, Zeng Q, Zhong S, Nie S, Zhang R, Hong H et al (2025) Association between choroid plexus morphological alterations, Alzheimer Pathologies, and cognitive impairment: a longitudinal study. Neurol 105:e213953. https:\/\/doi.org\/10.1212\/wnl.0000000000213953","journal-title":"Neurol"},{"key":"13997_CR29","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s12987-025-00729-7","volume":"22","author":"K Li","year":"2025","unstructured":"Li K, Qian W, Wang S, Sun Z, Zeng Q, Hong H et al (2025) Characterizing choroid plexus cyst burden across the Alzheimer\u2019s disease continuum. Fluids Barriers CNS 22:122. https:\/\/doi.org\/10.1186\/s12987-025-00729-7","journal-title":"Fluids Barriers CNS"},{"key":"13997_CR30","doi-asserted-by":"publisher","first-page":"112372","DOI":"10.1016\/j.ejrad.2025.112372","volume":"192","author":"Q Xie","year":"2025","unstructured":"Xie Q, Chen Z, Wang J, Wang Y, Zhang H, Wang X et al (2025) Enlarged choroid plexus is associated with reduced gray matter volumes and increased plasma amyloid-beta: a population-based study of older adults. Eur J Radiol 192:112372. https:\/\/doi.org\/10.1016\/j.ejrad.2025.112372","journal-title":"Eur J Radiol"},{"key":"13997_CR31","doi-asserted-by":"publisher","first-page":"3720","DOI":"10.1038\/s41467-023-39326-3","volume":"14","author":"RM Fame","year":"2023","unstructured":"Fame RM, Kalugin PN, Petrova B, Xu H, Soden PA, Shipley FB et al (2023) Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution. Nat Commun 14:3720. https:\/\/doi.org\/10.1038\/s41467-023-39326-3","journal-title":"Nat Commun"},{"key":"13997_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106100","volume":"181","author":"TJ Pedersen","year":"2023","unstructured":"Pedersen TJ, Keil SA, Han W, Wang MX, Iliff JJ (2023) The effect of aquaporin-4 mis-localization on A\u03b2 deposition in mice. Neurobiol Dis 181:106100. https:\/\/doi.org\/10.1016\/j.nbd.2023.106100","journal-title":"Neurobiol Dis"},{"key":"13997_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-97631-x","volume":"15","author":"GL Nozaleda","year":"2025","unstructured":"Nozaleda GL, Coenen W, Haughton V, S\u00e1nchez AL (2025) Arterial pulsations and transmantle pressure synergetically drive glymphatic flow. Sci Rep 15:13798. https:\/\/doi.org\/10.1038\/s41598-025-97631-x","journal-title":"Sci Rep"},{"key":"13997_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07318-3","volume":"9","author":"H Mestre","year":"2018","unstructured":"Mestre H, Tithof J, Du T, Song W, Peng W, Sweeney AM et al (2018) Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension. Nat Commun 9:4878. https:\/\/doi.org\/10.1038\/s41467-018-07318-3","journal-title":"Nat Commun"},{"key":"13997_CR35","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1038\/s41593-023-01327-2","volume":"26","author":"S Holstein-R\u00f8nsbo","year":"2023","unstructured":"Holstein-R\u00f8nsbo S, Gan Y, Giannetto MJ, Rasmussen MK, Sigurdsson B, Beinlich FRM et al (2023) Glymphatic influx and clearance are accelerated by neurovascular coupling. Nat Neurosci 26:1042\u20131053. https:\/\/doi.org\/10.1038\/s41593-023-01327-2","journal-title":"Nat Neurosci"},{"key":"13997_CR36","doi-asserted-by":"publisher","first-page":"2576","DOI":"10.1093\/brain\/awaa179","volume":"143","author":"IF Harrison","year":"2020","unstructured":"Harrison IF, Ismail O, Machhada A, Colgan N, Ohene Y, Nahavandi P et al (2020) Impaired glymphatic function and clearance of tau in an Alzheimer\u2019s disease model. Brain 143:2576\u20132593. https:\/\/doi.org\/10.1093\/brain\/awaa179","journal-title":"Brain"},{"key":"13997_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-022-00999-5","volume":"14","author":"M Simon","year":"2022","unstructured":"Simon M, Wang MX, Ismail O, Braun M, Schindler AG, Reemmer J et al (2022) Loss of perivascular aquaporin-4 localization impairs glymphatic exchange and promotes amyloid \u03b2 plaque formation in mice. Alzheimers Res Ther 14:59. https:\/\/doi.org\/10.1186\/s13195-022-00999-5","journal-title":"Alzheimers Res Ther"},{"key":"13997_CR38","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.jare.2023.03.004","volume":"56","author":"X Si","year":"2024","unstructured":"Si X, Dai S, Fang Y, Tang J, Wang Z, Li Y et al (2024) Matrix metalloproteinase-9 inhibition prevents aquaporin-4 depolarization-mediated glymphatic dysfunction in Parkinson\u2019s disease. J Adv Res 56:125\u2013136. https:\/\/doi.org\/10.1016\/j.jare.2023.03.004","journal-title":"J Adv Res"},{"key":"13997_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2024.109907","volume":"250","author":"J Li","year":"2024","unstructured":"Li J, Jia S, Song Y, Xu W, Lin J (2024) Ginkgolide B can alleviate spinal cord glymphatic system dysfunction and provide neuroprotection in painful diabetic neuropathy rats by inhibiting matrix metalloproteinase-9. Neuropharmacology 250:109907. https:\/\/doi.org\/10.1016\/j.neuropharm.2024.109907","journal-title":"Neuropharmacology"},{"key":"13997_CR40","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.70022","volume":"35","author":"Y Li","year":"2025","unstructured":"Li Y, Zhou H, Xie J, Yu M, Ye G, Zhang Y et al (2025) Targeting TRPV4 to restore glymphatic system function and alleviate cerebral edema in ischemic stroke. Brain Pathol 35:e70022. https:\/\/doi.org\/10.1111\/bpa.70022","journal-title":"Brain Pathol"},{"key":"13997_CR41","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-015-0056-1","volume":"10","author":"Z Xu","year":"2015","unstructured":"Xu Z, Xiao N, Chen Y, Huang H, Marshall C, Gao J et al (2015) Deletion of aquaporin-4 in APP\/PS1 mice exacerbates brain A\u03b2 accumulation and memory deficits. Mol Neurodegener 10:58. https:\/\/doi.org\/10.1186\/s13024-015-0056-1","journal-title":"Mol Neurodegener"},{"key":"13997_CR42","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2025.1621106","volume":"17","author":"F Chen","year":"2025","unstructured":"Chen F, Heng T, Feng Q, Hua R, Wu J, Shi F et al (2025) Quantitative assessment of brain glymphatic imaging features using deep learning-based EPVS segmentation and DTI-ALPS analysis in Alzheimer\u2019s disease. Front Aging Neurosci 17:1621106. https:\/\/doi.org\/10.3389\/fnagi.2025.1621106","journal-title":"Front Aging Neurosci"},{"key":"13997_CR43","doi-asserted-by":"publisher","first-page":"afaf141","DOI":"10.1093\/ageing\/afaf141","volume":"54","author":"Q Chen","year":"2025","unstructured":"Chen Q, Ge D, Xu X, Chen F, Du S, Bai Y et al (2025) Glymphatic function associates with Alzheimer\u2019s disease-signature region volumes, plasma biomarkers and white matter hyperintensity progression in cognitively unimpaired older adults. Age Ageing 54:afaf141. https:\/\/doi.org\/10.1093\/ageing\/afaf141","journal-title":"Age Ageing"},{"key":"13997_CR44","doi-asserted-by":"publisher","first-page":"3645","DOI":"10.1084\/jem.20170391","volume":"214","author":"S Antila","year":"2017","unstructured":"Antila S, Karaman S, Nurmi H, Airavaara M, Voutilainen MH, Mathivet T et al (2017) Development and plasticity of meningeal lymphatic vessels. J Exp Med 214:3645\u20133667. https:\/\/doi.org\/10.1084\/jem.20170391","journal-title":"J Exp Med"},{"key":"13997_CR45","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41586-021-03489-0","volume":"593","author":"S Da Mesquita","year":"2021","unstructured":"Da Mesquita S, Papadopoulos Z, Dykstra T, Brase L, Farias FG, Wall M et al (2021) Meningeal lymphatics affect microglia responses and anti-A\u03b2 immunotherapy. Nat 593:255\u2013260. https:\/\/doi.org\/10.1038\/s41586-021-03489-0","journal-title":"Nat"},{"key":"13997_CR46","doi-asserted-by":"publisher","first-page":"709","DOI":"10.4103\/1673-5374.230299","volume":"13","author":"YR Wen","year":"2018","unstructured":"Wen YR, Yang JH, Wang X, Yao ZB (2018) Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer\u2019s disease. Neural Regen Res 13:709\u2013716. https:\/\/doi.org\/10.4103\/1673-5374.230299","journal-title":"Neural Regen Res"},{"key":"13997_CR47","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1016\/j.stem.2023.09.012","volume":"30","author":"L Ma","year":"2023","unstructured":"Ma L, Chang Q, Pei F, Liu M, Zhang W, Hong YK et al (2023) Skull progenitor cell-driven meningeal lymphatic restoration improves neurocognitive functions in craniosynostosis. Cell Stem Cell 30:1472\u201385.e7. https:\/\/doi.org\/10.1016\/j.stem.2023.09.012","journal-title":"Cell Stem Cell"},{"key":"13997_CR48","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1038\/s41593-024-01604-8","volume":"27","author":"D Choi","year":"2024","unstructured":"Choi D, Park E, Choi J, Lu R, Yu JS, Kim C et al (2024) Piezo1 regulates meningeal lymphatic vessel drainage and alleviates excessive CSF accumulation. Nat Neurosci 27:913\u2013926. https:\/\/doi.org\/10.1038\/s41593-024-01604-8","journal-title":"Nat Neurosci"},{"key":"13997_CR49","doi-asserted-by":"publisher","first-page":"e171468","DOI":"10.1172\/jci171468","volume":"134","author":"MJ Matrongolo","year":"2023","unstructured":"Matrongolo MJ, Ang PS, Wu J, Jain A, Thackray JK, Reddy A et al (2023) Piezo1 agonist restores meningeal lymphatic vessels, drainage, and brain-CSF perfusion in craniosynostosis and aged mice. J Clin Invest 134:e171468. https:\/\/doi.org\/10.1172\/jci171468","journal-title":"J Clin Invest"},{"key":"13997_CR50","doi-asserted-by":"publisher","first-page":"e176858","DOI":"10.1172\/jci176858","volume":"134","author":"A Aspelund","year":"2024","unstructured":"Aspelund A, Alitalo K (2024) Yoda1 opens the lymphatic path for craniosynostosis therapy. J Clin Invest 134:e176858. https:\/\/doi.org\/10.1172\/jci176858","journal-title":"J Clin Invest"},{"key":"13997_CR51","doi-asserted-by":"publisher","first-page":"e2","DOI":"10.1161\/circresaha.121.320565","volume":"131","author":"D Choi","year":"2022","unstructured":"Choi D, Park E, Yu RP, Cooper MN, Cho IT, Choi J et al (2022) Piezo1-regulated Mechanotransduction controls flow-activated lymphatic expansion. Circ Res 131:e2\u2013e21. https:\/\/doi.org\/10.1161\/circresaha.121.320565","journal-title":"Circ Res"},{"key":"13997_CR52","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s41586-019-1419-5","volume":"572","author":"JH Ahn","year":"2019","unstructured":"Ahn JH, Cho H, Kim JH, Kim SH, Ham JS, Park I et al (2019) Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid. Nat 572:62\u201366. https:\/\/doi.org\/10.1038\/s41586-019-1419-5","journal-title":"Nat"},{"key":"13997_CR53","doi-asserted-by":"publisher","first-page":"e101641","DOI":"10.1136\/gpsych-2024-101641","volume":"37","author":"X Li","year":"2024","unstructured":"Li X, Zhang C, Fang Y, Xin M, Shi J, Zhang Z et al (2024) Promising outcomes 5 weeks after a surgical cervical shunting procedure to unclog cerebral lymphatic systems in a patient with Alzheimer\u2019s disease. Gen Psychiatr 37:e101641. https:\/\/doi.org\/10.1136\/gpsych-2024-101641","journal-title":"Gen Psychiatr"},{"key":"13997_CR54","doi-asserted-by":"publisher","first-page":"4211","DOI":"10.1097\/js9.0000000000002490","volume":"111","author":"JY Chen","year":"2025","unstructured":"Chen JY, Zhao DW, Yin Y, Gui L, Chen X, Wang XM et al (2025) Deep cervical lymphovenous anastomosis (LVA) for Alzheimer\u2019s disease: microsurgical procedure in a prospective cohort study. Int J Surg 111:4211\u20134221. https:\/\/doi.org\/10.1097\/js9.0000000000002490","journal-title":"Int J Surg"},{"key":"13997_CR55","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1126\/science.1241224","volume":"342","author":"L Xie","year":"2013","unstructured":"Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M et al (2013) Sleep drives metabolite clearance from the adult brain. Sci 342:373\u2013377. https:\/\/doi.org\/10.1126\/science.1241224","journal-title":"Sci"},{"key":"13997_CR56","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s12987-021-00296-7","volume":"18","author":"M Muccio","year":"2021","unstructured":"Muccio M, Chu D, Minkoff L, Kulkarni N, Damadian B, Damadian RV et al (2021) Upright versus supine MRI: effects of body position on craniocervical CSF flow. Fluids Barriers CNS 18:61. https:\/\/doi.org\/10.1186\/s12987-021-00296-7","journal-title":"Fluids Barriers CNS"},{"key":"13997_CR57","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20220035","author":"L Jacob","year":"2022","unstructured":"Jacob L, de Brito Neto J, Lenck S, Corcy C, Benbelkacem F, Geraldo LH et al (2022) Conserved meningeal lymphatic drainage circuits in mice and humans. J Exp Med. https:\/\/doi.org\/10.1084\/jem.20220035","journal-title":"J Exp Med"},{"key":"13997_CR58","doi-asserted-by":"publisher","first-page":"1228344","DOI":"10.3389\/fcell.2023.1228344","volume":"11","author":"CL Vera Quesada","year":"2023","unstructured":"Vera Quesada CL, Rao SB, Torp R, Eide PK (2023) Widespread distribution of lymphatic vessels in human dura mater remote from sinus veins. Front Cell Dev Biol 11:1228344. https:\/\/doi.org\/10.3389\/fcell.2023.1228344","journal-title":"Front Cell Dev Biol"},{"key":"13997_CR59","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1038\/s41586-023-06899-4","volume":"625","author":"JH Yoon","year":"2024","unstructured":"Yoon JH, Jin H, Kim HJ, Hong SP, Yang MJ, Ahn JH et al (2024) Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage. Nat 625:768\u2013777. https:\/\/doi.org\/10.1038\/s41586-023-06899-4","journal-title":"Nat"},{"key":"13997_CR60","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1002\/ana.26516","volume":"93","author":"JL Hsu","year":"2023","unstructured":"Hsu JL, Wei YC, Toh CH, Hsiao IT, Lin KJ, Yen TC et al (2023) Magnetic resonance images implicate that glymphatic alterations mediate cognitive dysfunction in Alzheimer disease. Ann Neurol 93:164\u2013174. https:\/\/doi.org\/10.1002\/ana.26516","journal-title":"Ann Neurol"},{"key":"13997_CR61","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1007\/s11604-017-0617-z","volume":"35","author":"T Taoka","year":"2017","unstructured":"Taoka T, Masutani Y, Kawai H, Nakane T, Matsuoka K, Yasuno F et al (2017) 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. Jpn J Radiol 35:172\u2013178. https:\/\/doi.org\/10.1007\/s11604-017-0617-z","journal-title":"Jpn J Radiol"},{"key":"13997_CR62","doi-asserted-by":"publisher","first-page":"268","DOI":"10.2463\/mrms.rev.2023-0175","volume":"23","author":"T Taoka","year":"2024","unstructured":"Taoka T, Ito R, Nakamichi R, Nakane T, Kawai H, Naganawa S (2024) Diffusion tensor image analysis ALong the Perivascular space (DTI-ALPS): revisiting the meaning and significance of the method. Magn Reson Med Sci 23:268\u2013290. https:\/\/doi.org\/10.2463\/mrms.rev.2023-0175","journal-title":"Magn Reson Med Sci"},{"key":"13997_CR63","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s00234-023-03270-2","volume":"66","author":"G Ringstad","year":"2024","unstructured":"Ringstad G (2024) Glymphatic imaging: a critical look at the DTI-ALPS index. Neuroradiol 66:157\u2013160. https:\/\/doi.org\/10.1007\/s00234-023-03270-2","journal-title":"Neuroradiol"},{"key":"13997_CR64","doi-asserted-by":"publisher","first-page":"fcae421","DOI":"10.1093\/braincomms\/fcae421","volume":"6","author":"C Georgiopoulos","year":"2024","unstructured":"Georgiopoulos C, Werlin A, Lasic S, Hall S, van Westen D, Spotorno N et al (2024) Diffusion tensor imaging along the perivascular space: the bias from crossing fibres. Brain Commun 6:fcae421. https:\/\/doi.org\/10.1093\/braincomms\/fcae421","journal-title":"Brain Commun"},{"key":"13997_CR65","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awag080","author":"N Liu","year":"2026","unstructured":"Liu N, Yang Y, Kritsilis M, Swanberg KM, Liu C, Liu X et al (2026) Early glymphatic failure in AppNL-F knock-in mice is linked to parenchymal border macrophages loss. Brain. https:\/\/doi.org\/10.1093\/brain\/awag080","journal-title":"Brain"},{"key":"13997_CR66","doi-asserted-by":"publisher","first-page":"2799","DOI":"10.1007\/s00259-025-07716-y","volume":"53","author":"K He","year":"2026","unstructured":"He K, Wang J, Wu J, Chen X, Chen H, Li J et al (2026) Impaired glymphatic function is associated with synaptic loss in cognitive impairment. Eur J Nucl Med Mol Imaging 53:2799\u20132810. https:\/\/doi.org\/10.1007\/s00259-025-07716-y","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"13997_CR67","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/s41586-018-0368-8","volume":"560","author":"S Da Mesquita","year":"2018","unstructured":"Da Mesquita S, Louveau A, Vaccari A, Smirnov I, Cornelison RC, Kingsmore KM et al (2018) Functional aspects of meningeal lymphatics in ageing and Alzheimer\u2019s disease. Nat 560:185\u2013191. https:\/\/doi.org\/10.1038\/s41586-018-0368-8","journal-title":"Nat"},{"key":"13997_CR68","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jalz.2012.11.007","volume":"9","author":"M Prince","year":"2013","unstructured":"Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP (2013) The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 9:63-75.e2. https:\/\/doi.org\/10.1016\/j.jalz.2012.11.007","journal-title":"Alzheimers Dement"},{"key":"13997_CR69","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106426","volume":"192","author":"Y Cai","year":"2024","unstructured":"Cai Y, Zhang Y, Leng S, Ma Y, Jiang Q, Wen Q et al (2024) The relationship between inflammation, impaired glymphatic system, and neurodegenerative disorders: a vicious cycle. Neurobiol Dis 192:106426. https:\/\/doi.org\/10.1016\/j.nbd.2024.106426","journal-title":"Neurobiol Dis"},{"key":"13997_CR70","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s13024-023-00645-0","volume":"18","author":"S Rego","year":"2023","unstructured":"Rego S, Sanchez G, Da Mesquita S (2023) Current views on meningeal lymphatics and immunity in aging and Alzheimer\u2019s disease. Mol Neurodegener 18:55. https:\/\/doi.org\/10.1186\/s13024-023-00645-0","journal-title":"Mol Neurodegener"},{"key":"13997_CR71","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176336","author":"MF Lanfranco","year":"2020","unstructured":"Lanfranco MF, Ng CA, Rebeck GW (2020) ApoE lipidation as a therapeutic target in Alzheimer\u2019s disease. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms21176336","journal-title":"Int J Mol Sci"},{"key":"13997_CR72","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.2353\/ajpath.2009.080963","volume":"175","author":"HY Lim","year":"2009","unstructured":"Lim HY, Rutkowski JM, Helft J, Reddy ST, Swartz MA, Randolph GJ et al (2009) Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration. Am J Pathol 175:1328\u20131337. https:\/\/doi.org\/10.2353\/ajpath.2009.080963","journal-title":"Am J Pathol"},{"key":"13997_CR73","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-016-0138-8","volume":"11","author":"TM Achariyar","year":"2016","unstructured":"Achariyar TM, Li B, Peng W, Verghese PB, Shi Y, McConnell E et al (2016) Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation. Mol Neurodegener 11:74. https:\/\/doi.org\/10.1186\/s13024-016-0138-8","journal-title":"Mol Neurodegener"},{"key":"13997_CR74","doi-asserted-by":"publisher","first-page":"e70837","DOI":"10.1002\/alz.70837","volume":"21","author":"KM Kang","year":"2025","unstructured":"Kang KM, Park C, Byun MS, Yi D, Nam H, Ryu J et al (2025) APOE4 modulates the association between DTI-ALPS index and Alzheimer\u2019s pathologies. Alzheimers Dement 21:e70837. https:\/\/doi.org\/10.1002\/alz.70837","journal-title":"Alzheimers Dement"},{"key":"13997_CR75","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1038\/s41380-020-0731-7","volume":"26","author":"AA Mentis","year":"2021","unstructured":"Mentis AA, Dardiotis E, Chrousos GP (2021) Apolipoprotein E4 and meningeal lymphatics in Alzheimer disease: a conceptual framework. Mol Psychiatry 26:1075\u20131097. https:\/\/doi.org\/10.1038\/s41380-020-0731-7","journal-title":"Mol Psychiatry"},{"key":"13997_CR76","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/s41398-022-01897-y","volume":"12","author":"Y Zhang","year":"2022","unstructured":"Zhang Y, Ren R, Yang L, Zhang H, Shi Y, Okhravi HR et al (2022) Sleep in Alzheimer\u2019s disease: a systematic review and meta-analysis of polysomnographic findings. Transl Psychiatry 12:136. https:\/\/doi.org\/10.1038\/s41398-022-01897-y","journal-title":"Transl Psychiatry"},{"key":"13997_CR77","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1126\/science.aax5440","volume":"366","author":"NE Fultz","year":"2019","unstructured":"Fultz NE, Bonmassar G, Setsompop K, Stickgold RA, Rosen BR, Polimeni JR et al (2019) Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science 366:628\u2013631. https:\/\/doi.org\/10.1126\/science.aax5440","journal-title":"Science"},{"key":"13997_CR78","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1093\/brain\/awaa443","volume":"144","author":"PK Eide","year":"2021","unstructured":"Eide PK, Vinje V, Pripp AH, Mardal KA, Ringstad G (2021) Sleep deprivation impairs molecular clearance from the human brain. Brain 144:863\u2013874. https:\/\/doi.org\/10.1093\/brain\/awaa443","journal-title":"Brain"},{"key":"13997_CR79","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1097\/aln.0000000000001888","volume":"127","author":"H Benveniste","year":"2017","unstructured":"Benveniste H, Lee H, Ding F, Sun Q, Al-Bizri E, Makaryus R et al (2017) Anesthesia with Dexmedetomidine and low-dose isoflurane increases solute transport via the Glymphatic pathway in rat brain when compared with high-dose isoflurane. Anesthesiol 127:976\u2013988. https:\/\/doi.org\/10.1097\/aln.0000000000001888","journal-title":"Anesthesiol"},{"key":"13997_CR80","doi-asserted-by":"publisher","first-page":"eaav5447","DOI":"10.1126\/sciadv.aav5447","volume":"5","author":"LM Hablitz","year":"2019","unstructured":"Hablitz LM, Vinitsky HS, Sun Q, St\u00e6ger FF, Sigurdsson B, Mortensen KN et al (2019) Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia. Sci Adv 5:eaav5447. https:\/\/doi.org\/10.1126\/sciadv.aav5447","journal-title":"Sci Adv"},{"key":"13997_CR81","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.cell.2024.11.027","volume":"188","author":"NL Hauglund","year":"2025","unstructured":"Hauglund NL, Andersen M, Tokarska K, Radovanovic T, Kjaerby C, S\u00f8rensen FL et al (2025) Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep. Cell 188:606\u201322.e17. https:\/\/doi.org\/10.1016\/j.cell.2024.11.027","journal-title":"Cell"},{"key":"13997_CR82","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1038\/s41593-024-01638-y","volume":"27","author":"A Miao","year":"2024","unstructured":"Miao A, Luo T, Hsieh B, Edge CJ, Gridley M, Wong RTC et al (2024) Brain clearance is reduced during sleep and anesthesia. Nat Neurosci 27:1046\u20131050. https:\/\/doi.org\/10.1038\/s41593-024-01638-y","journal-title":"Nat Neurosci"},{"key":"13997_CR83","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsy025","author":"M Olsson","year":"2018","unstructured":"Olsson M, \u00c4rlig J, Hedner J, Blennow K, Zetterberg H (2018) Sleep deprivation and cerebrospinal fluid biomarkers for Alzheimer\u2019s disease. Sleep. https:\/\/doi.org\/10.1093\/sleep\/zsy025","journal-title":"Sleep"},{"key":"13997_CR84","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-026-03691-9","author":"F Tang","year":"2026","unstructured":"Tang F, Li Y, Bai X, Zhu Z, Dong H, Chen J et al (2026) BMAL1-GPX3 axis in the choroid plexus mitigates A\u03b2 pathology in an amyloid mouse model. J Neuroinflammation. https:\/\/doi.org\/10.1186\/s12974-026-03691-9","journal-title":"J Neuroinflammation"},{"key":"13997_CR85","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2023.105633","author":"X Zhang","year":"2023","unstructured":"Zhang X, Cao R, Zhu C, Yang L, Zheng N, Ji W et al (2023) Mechanism of anti-AD action of OAB-14 by enhancing the function of glymphatic system. Neurochem Int. https:\/\/doi.org\/10.1016\/j.neuint.2023.105633","journal-title":"Neurochem Int"},{"key":"13997_CR86","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1007\/s11064-025-04388-w","volume":"50","author":"X Zhao","year":"2025","unstructured":"Zhao X, Cao R, Tian X, Liu P, Liu D, Yu X et al (2025) OAB-14 attenuated glymphatic system disorder, neuroinflammation and dyskinesia in Parkinson\u2019s disease model mice induced by rotenone. Neurochem Res 50:142. https:\/\/doi.org\/10.1007\/s11064-025-04388-w","journal-title":"Neurochem Res"},{"key":"13997_CR87","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14669","volume":"30","author":"D Feng","year":"2024","unstructured":"Feng D, Liu T, Zhang X, Xiang T, Su W, Quan W et al (2024) Fingolimod improves diffuse brain injury by promoting AQP4 polarization and functional recovery of the glymphatic system. CNS Neurosci Ther 30:e14669. https:\/\/doi.org\/10.1111\/cns.14669","journal-title":"CNS Neurosci Ther"},{"key":"13997_CR88","doi-asserted-by":"publisher","first-page":"11443","DOI":"10.1007\/s12035-025-04992-5","volume":"62","author":"H Sun","year":"2025","unstructured":"Sun H, Cao Q, He X, Du X, Jiang X, Wu T et al (2025) Melatonin mitigates sleep restriction-induced cognitive and glymphatic dysfunction via aquaporin-4 polarization. Mol Neurobiol 62:11443\u201311465. https:\/\/doi.org\/10.1007\/s12035-025-04992-5","journal-title":"Mol Neurobiol"},{"key":"13997_CR89","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/s41398-023-02614-z","volume":"13","author":"D Yao","year":"2023","unstructured":"Yao D, Li R, Hao J, Huang H, Wang X, Ran L et al (2023) Melatonin alleviates depression-like behaviors and cognitive dysfunction in mice by regulating the circadian rhythm of AQP4 polarization. Transl Psychiatry 13:310. https:\/\/doi.org\/10.1038\/s41398-023-02614-z","journal-title":"Transl Psychiatry"},{"key":"13997_CR90","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.883503","volume":"14","author":"XL Liu","year":"2022","unstructured":"Liu XL, Ouyang FB, Hu LT, Sun P, Yang J, Sun YJ et al (2022) 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. Front Aging Neurosci 14:883503. https:\/\/doi.org\/10.3389\/fnagi.2022.883503","journal-title":"Front Aging Neurosci"},{"key":"13997_CR91","doi-asserted-by":"publisher","first-page":"5640","DOI":"10.3390\/ijms24065640","volume":"24","author":"M Garc\u00eda-Bonilla","year":"2023","unstructured":"Garc\u00eda-Bonilla M, Ojeda-P\u00e9rez B, Shumilov K, Rodr\u00edguez-P\u00e9rez LM, Dom\u00ednguez-Pinos D, Vitorica J et al (2023) Generation of periventricular reactive astrocytes overexpressing aquaporin 4 is stimulated by mesenchymal stem cell therapy. Int J Mol Sci 24:5640. https:\/\/doi.org\/10.3390\/ijms24065640","journal-title":"Int J Mol Sci"},{"key":"13997_CR92","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/nature20587","volume":"540","author":"HF Iaccarino","year":"2016","unstructured":"Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ et al (2016) Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nat 540:230\u2013235. https:\/\/doi.org\/10.1038\/nature20587","journal-title":"Nat"},{"key":"13997_CR93","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/s41586-024-07132-6","volume":"627","author":"MH Murdock","year":"2024","unstructured":"Murdock MH, Yang CY, Sun N, Pao PC, Blanco-Duque C, Kahn MC et al (2024) Multisensory gamma stimulation promotes glymphatic clearance of amyloid. Nat 627:149\u2013156. https:\/\/doi.org\/10.1038\/s41586-024-07132-6","journal-title":"Nat"},{"key":"13997_CR94","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/s41421-024-00701-z","volume":"10","author":"X Sun","year":"2024","unstructured":"Sun X, Dias L, Peng C, Zhang Z, Ge H, Wang Z et al (2024) 40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice. Cell Discov 10:81. https:\/\/doi.org\/10.1038\/s41421-024-00701-z","journal-title":"Cell Discov"},{"key":"13997_CR95","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41467-024-55678-w","volume":"16","author":"W Wu","year":"2025","unstructured":"Wu W, Zhao Y, Cheng X, Xie X, Zeng Y, Tao Q et al (2025) Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer\u2019s disease. Nat Commun 16:63. https:\/\/doi.org\/10.1038\/s41467-024-55678-w","journal-title":"Nat Commun"},{"key":"13997_CR96","doi-asserted-by":"publisher","first-page":"16206","DOI":"10.1038\/s41598-021-95550-1","volume":"11","author":"K Lee","year":"2021","unstructured":"Lee K, Park Y, Suh SW, Kim SS, Kim DW, Lee J et al (2021) Optimal flickering light stimulation for entraining gamma waves in the human brain. Sci Rep 11:16206. https:\/\/doi.org\/10.1038\/s41598-021-95550-1","journal-title":"Sci Rep"},{"key":"13997_CR97","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s40478-021-01198-3","volume":"9","author":"Y Lin","year":"2021","unstructured":"Lin Y, Jin J, Lv R, Luo Y, Dai W, Li W et al (2021) Repetitive transcranial magnetic stimulation increases the brain\u2019s drainage efficiency in a mouse model of Alzheimer\u2019s disease. Acta Neuropathol Commun 9:102. https:\/\/doi.org\/10.1186\/s40478-021-01198-3","journal-title":"Acta Neuropathol Commun"},{"key":"13997_CR98","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2140524","author":"C Wu","year":"2022","unstructured":"Wu C, Lin T, Ding Q, Zhang N, Ou ZT, Cai GY et al (2022) Continuous theta-burst stimulation promotes paravascular CSF-interstitial fluid exchange through regulation of aquaporin-4 polarization in APP\/PS1 mice. Mediators Inflamm. https:\/\/doi.org\/10.1155\/2022\/2140524","journal-title":"Mediators Inflamm"},{"key":"13997_CR99","doi-asserted-by":"publisher","DOI":"10.1186\/s12984-025-01738-1","volume":"22","author":"CC Yang","year":"2025","unstructured":"Yang CC, Huang KY, Hsu JL, Hu CJ, Lu YH, Kuan YC (2025) Effects of intermittent theta-burst stimulation on cognition and glymphatic system activity in mild cognitive impairment and very mild Alzheimer\u2019s disease: a randomized controlled trial. J Neuroeng Rehabil 22:195. https:\/\/doi.org\/10.1186\/s12984-025-01738-1","journal-title":"J Neuroeng Rehabil"},{"key":"13997_CR100","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s12987-023-00447-y","volume":"20","author":"RI Mehta","year":"2023","unstructured":"Mehta RI, Carpenter JS, Mehta RI, Haut MW, Wang P, Ranjan M et al (2023) Ultrasound-mediated blood\u2013brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer\u2019s disease. Fluids Barriers CNS 20:46. https:\/\/doi.org\/10.1186\/s12987-023-00447-y","journal-title":"Fluids Barriers CNS"},{"key":"13997_CR101","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2212933120","volume":"120","author":"D Ye","year":"2023","unstructured":"Ye D, Chen S, Liu Y, Weixel C, Hu Z, Yuan J et al (2023) Mechanically manipulating glymphatic transport by ultrasound combined with microbubbles. Proc Natl Acad Sci U S A 120:e2212933120. https:\/\/doi.org\/10.1073\/pnas.2212933120","journal-title":"Proc Natl Acad Sci U S A"},{"key":"13997_CR102","doi-asserted-by":"publisher","first-page":"3191","DOI":"10.3390\/biomedicines10123191","volume":"10","author":"HJ Choi","year":"2022","unstructured":"Choi HJ, Han M, Jung B, Hong YR, Shin S, Lim S et al (2022) Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood-Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation. Biomed 10:3191. https:\/\/doi.org\/10.3390\/biomedicines10123191","journal-title":"Biomed"},{"key":"13997_CR103","doi-asserted-by":"publisher","first-page":"e2401039","DOI":"10.1002\/advs.202401039","volume":"11","author":"CH Wu","year":"2024","unstructured":"Wu CH, Liao WH, Chu YC, Hsiao MY, Kung Y, Wang JL et al (2024) Very Low-Intensity Ultrasound Facilitates Glymphatic Influx and clearance via modulation of the TRPV4-AQP4 Pathway. Adv Sci (Weinh) 11:e2401039. https:\/\/doi.org\/10.1002\/advs.202401039","journal-title":"Adv Sci (Weinh)"},{"key":"13997_CR104","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.brs.2024.09.006","volume":"17","author":"S Choi","year":"2024","unstructured":"Choi S, Kum J, Hyun SY, Park TY, Kim H, Kim SK et al (2024) Transcranial focused ultrasound stimulation enhances cerebrospinal fluid movement: Real-time in vivo two-photon and widefield imaging evidence. Brain Stimul 17:1119\u20131130. https:\/\/doi.org\/10.1016\/j.brs.2024.09.006","journal-title":"Brain Stimul"},{"key":"13997_CR105","doi-asserted-by":"publisher","first-page":"3434","DOI":"10.7150\/thno.81951","volume":"13","author":"S Feng","year":"2023","unstructured":"Feng S, Wu C, Zou P, Deng Q, Chen Z, Li M et al (2023) High-intensity interval training ameliorates Alzheimer\u2019s disease-like pathology by regulating astrocyte phenotype-associated AQP4 polarization. Theranostics 13:3434\u20133450. https:\/\/doi.org\/10.7150\/thno.81951","journal-title":"Theranostics"},{"key":"13997_CR106","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.4103\/1673-5374.335169","volume":"17","author":"Y Liu","year":"2022","unstructured":"Liu Y, Hu PP, Zhai S, Feng WX, Zhang R, Li Q et al (2022) Aquaporin 4 deficiency eliminates the beneficial effects of voluntary exercise in a mouse model of Alzheimer\u2019s disease. Neural Regen Res 17:2079\u20132088. https:\/\/doi.org\/10.4103\/1673-5374.335169","journal-title":"Neural Regen Res"},{"key":"13997_CR107","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3390\/ph14020086","volume":"14","author":"L Ciccone","year":"2021","unstructured":"Ciccone L, Vandooren J, Nencetti S, Orlandini E (2021) Natural Marine and Terrestrial Compounds as Modulators of Matrix Metalloproteinases-2 (MMP-2) and MMP-9 in Alzheimer\u2019s Disease. Pharm (Basel) 14:86. https:\/\/doi.org\/10.3390\/ph14020086","journal-title":"Pharm (Basel)"},{"key":"13997_CR108","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3389\/fphar.2019.00086","volume":"10","author":"KT Chen","year":"2019","unstructured":"Chen KT, Wei KC, Liu HL (2019) Theranostic strategy of focused ultrasound induced blood-brain barrier opening for CNS disease treatment. Front Pharmacol 10:86. https:\/\/doi.org\/10.3389\/fphar.2019.00086","journal-title":"Front Pharmacol"},{"key":"13997_CR109","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1007\/s12975-024-01262-9","volume":"16","author":"MH Keuters","year":"2025","unstructured":"Keuters MH, Antila S, Immonen R, Plotnikova L, Wojciechowski S, Lehtonen S et al (2025) The impact of VEGF-C-Induced Dural Lymphatic vessel growth on ischemic stroke pathology. Transl Stroke Res 16:781\u2013799. https:\/\/doi.org\/10.1007\/s12975-024-01262-9","journal-title":"Transl Stroke Res"},{"key":"13997_CR110","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1002\/path.5767","volume":"255","author":"C Choi","year":"2021","unstructured":"Choi C, Park J, Kim H, Chang KT, Park J, Min KT (2021) DSCR1 upregulation enhances dural meningeal lymphatic drainage to attenuate amyloid pathology of Alzheimer\u2019s disease. J Pathol 255:296\u2013310. https:\/\/doi.org\/10.1002\/path.5767","journal-title":"J Pathol"},{"key":"13997_CR111","doi-asserted-by":"publisher","first-page":"4331","DOI":"10.7150\/thno.98587","volume":"14","author":"C Ye","year":"2024","unstructured":"Ye C, Wang S, Niu L, Yang F, Wang G, Wang S et al (2024) Unlocking potential of oxytocin: improving intracranial lymphatic drainage for Alzheimer\u2019s disease treatment. Theranostics 14:4331\u20134351. https:\/\/doi.org\/10.7150\/thno.98587","journal-title":"Theranostics"},{"key":"13997_CR112","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1038\/s41467-024-45656-7","volume":"15","author":"M Wang","year":"2024","unstructured":"Wang M, Yan C, Li X, Yang T, Wu S, Liu Q et al (2024) Non-invasive modulation of meningeal lymphatics ameliorates ageing and Alzheimer\u2019s disease-associated pathology and cognition in mice. Nat Commun 15:1453. https:\/\/doi.org\/10.1038\/s41467-024-45656-7","journal-title":"Nat Commun"},{"key":"13997_CR113","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s12200-023-00080-5","volume":"16","author":"SG Oxana","year":"2023","unstructured":"Oxana SG, Alexander S, Inna B, Ivan F, Andrey T, Alexander D et al (2023) Mechanisms of phototherapy of Alzheimer\u2019s disease during sleep and wakefulness: the role of the meningeal lymphatics. Front Optoelectron 16:22. https:\/\/doi.org\/10.1007\/s12200-023-00080-5","journal-title":"Front Optoelectron"},{"key":"13997_CR114","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s12200-023-00099-8","volume":"16","author":"D Li","year":"2023","unstructured":"Li D, Lin H, Sun S, Liu S, Liu Z, He Y et al (2023) Photostimulation of lymphatic clearance of \u03b2-amyloid from mouse brain: a new strategy for the therapy of Alzheimer\u2019s disease. Front Optoelectron 16:45. https:\/\/doi.org\/10.1007\/s12200-023-00099-8","journal-title":"Front Optoelectron"},{"key":"13997_CR115","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s40035-025-00497-2","volume":"14","author":"Y Chen","year":"2025","unstructured":"Chen Y, Cai J, She Y, He X, Feng H, Li X et al (2025) Long-term exercise enhances meningeal lymphatic vessel plasticity and drainage in a mouse model of Alzheimer\u2019s disease. Transl Neurodegener 14:37. https:\/\/doi.org\/10.1186\/s40035-025-00497-2","journal-title":"Transl Neurodegener"},{"key":"13997_CR116","doi-asserted-by":"publisher","first-page":"3360","DOI":"10.1038\/s41467-025-58726-1","volume":"16","author":"RE Yoo","year":"2025","unstructured":"Yoo RE, Kim JH, Moon HY, Park JY, Cheon S, Shin HS et al (2025) Long-term physical exercise facilitates putative glymphatic and meningeal lymphatic vessel flow in humans. Nat Commun 16:3360. https:\/\/doi.org\/10.1038\/s41467-025-58726-1","journal-title":"Nat Commun"},{"key":"13997_CR117","doi-asserted-by":"publisher","DOI":"10.1097\/js9.0000000000004561","author":"C Tang","year":"2025","unstructured":"Tang C, Zheng X, Li H, Wang B, Zheng Y, Song W et al (2025) Deep cervical lymphatic-venous anastomosis in dementia: a clinical and mechanistic evaluation. Int J Surg. https:\/\/doi.org\/10.1097\/js9.0000000000004561","journal-title":"Int J Surg"},{"key":"13997_CR118","doi-asserted-by":"publisher","first-page":"6441","DOI":"10.1021\/acs.jmedchem.2c00085","volume":"65","author":"H Tang","year":"2022","unstructured":"Tang H, Zeng R, He E, Zhang I, Ding C, Zhang A (2022) Piezo-Type Mechanosensitive Ion Channel Component 1 (Piezo1): A Promising Therapeutic Target and Its Modulators. J Med Chem 65:6441\u20136453. https:\/\/doi.org\/10.1021\/acs.jmedchem.2c00085","journal-title":"J Med Chem"},{"key":"13997_CR119","doi-asserted-by":"publisher","first-page":"8329","DOI":"10.1038\/ncomms9329","volume":"6","author":"V Lukacs","year":"2015","unstructured":"Lukacs V, Mathur J, Mao R, Bayrak-Toydemir P, Procter M, Cahalan SM et al (2015) Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia. Nat Commun 6:8329. https:\/\/doi.org\/10.1038\/ncomms9329","journal-title":"Nat Commun"},{"key":"13997_CR120","doi-asserted-by":"publisher","first-page":"8085","DOI":"10.1038\/ncomms9085","volume":"6","author":"E Fotiou","year":"2015","unstructured":"Fotiou E, Martin-Almedina S, Simpson MA, Lin S, Gordon K, Brice G et al (2015) Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. Nat Commun 6:8085. https:\/\/doi.org\/10.1038\/ncomms9085","journal-title":"Nat Commun"},{"key":"13997_CR121","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s00415-022-11454-8","volume":"270","author":"S L\u00f3pez-Ortiz","year":"2023","unstructured":"L\u00f3pez-Ortiz S, Lista S, Valenzuela PL, Pinto-Fraga J, Carmona R, Caraci F et al (2023) Effects of physical activity and exercise interventions on Alzheimer\u2019s disease: an umbrella review of existing meta-analyses. J Neurol 270:711\u2013725. https:\/\/doi.org\/10.1007\/s00415-022-11454-8","journal-title":"J Neurol"},{"key":"13997_CR122","doi-asserted-by":"publisher","first-page":"e71150","DOI":"10.1002\/alz.71150","volume":"22","author":"X Fu","year":"2026","unstructured":"Fu X, Zhang J, Xiao Q, Li T, Li Q, Zhang S et al (2026) Deep cervical lymphatic-venous anastomosis attenuates cognitive dysfunction and biomarker abnormalities in severe Alzheimer\u2019s disease: a prospective single-arm study. Alzheimers Dement 22:e71150. https:\/\/doi.org\/10.1002\/alz.71150","journal-title":"Alzheimers Dement"},{"key":"13997_CR123","doi-asserted-by":"publisher","first-page":"100335","DOI":"10.1016\/j.tjpad.2025.100335","volume":"13","author":"T Lahmar","year":"2026","unstructured":"Lahmar T, Thuau F, Pinard G, Boutoleau-Bretonniere C, Perrot P, Lancien U (2026) Brain lymphatic drainage pathways, deep cervical lymphatic surgery, and current insights: a systematic review. J Prev Alzheimers Dis 13:100335. https:\/\/doi.org\/10.1016\/j.tjpad.2025.100335","journal-title":"J Prev Alzheimers Dis"},{"key":"13997_CR124","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41593-025-01897-3","volume":"28","author":"V Pl\u00e1","year":"2025","unstructured":"Pl\u00e1 V, Kroesbergen E, Deng S, Giannetto MJ, Hablitz LM, Newbold E et al (2025) A curious concept of CNS clearance. Nat Neurosci 28:731\u2013733. https:\/\/doi.org\/10.1038\/s41593-025-01897-3","journal-title":"Nat Neurosci"},{"key":"13997_CR125","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1021\/acs.nanolett.5c04420","volume":"26","author":"YN Ding","year":"2026","unstructured":"Ding YN, Li MQ, Ding PT, Wang P, Guan PP (2026) Complement C1q-targeted microglial membrane camouflaged nanolipid carriers for synaptic protection in Alzheimer\u2019s disease: a bioinspired alectinib delivery strategy. Nano Lett 26:1181\u20131191. https:\/\/doi.org\/10.1021\/acs.nanolett.5c04420","journal-title":"Nano Lett"},{"key":"13997_CR126","doi-asserted-by":"publisher","first-page":"10632","DOI":"10.3390\/ijms251910632","volume":"25","author":"M Menendez-Gonzalez","year":"2024","unstructured":"Menendez-Gonzalez M (2024) Intrathecal Immunoselective Nanopheresis for Alzheimer\u2019s disease: what and How? Why and When? Int J Mol Sci 25:10632. https:\/\/doi.org\/10.3390\/ijms251910632","journal-title":"Int J Mol Sci"},{"key":"13997_CR127","doi-asserted-by":"publisher","first-page":"115323","DOI":"10.1016\/j.addr.2024.115323","volume":"209","author":"P Zhao","year":"2024","unstructured":"Zhao P, Wu T, Tian Y, You J, Cui X (2024) Recent advances of focused ultrasound induced blood\u2013brain barrier opening for clinical applications of neurodegenerative diseases. Adv Drug Deliv Rev 209:115323. https:\/\/doi.org\/10.1016\/j.addr.2024.115323","journal-title":"Adv Drug Deliv Rev"},{"key":"13997_CR128","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-026-13954-3","author":"Y Chen","year":"2026","unstructured":"Chen Y, Wang Z, Chen H, Li H, Zhang Z, Cui H et al (2026) Plasma p-Tau217 and A\u03b242\/A\u03b240 mediate the association between minimal depressive symptoms and cognitive impairment. J Neurol. https:\/\/doi.org\/10.1007\/s00415-026-13954-3","journal-title":"J Neurol"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-13997-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-026-13997-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-13997-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T07:49:02Z","timestamp":1786348142000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-026-13997-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":128,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["13997"],"URL":"https:\/\/doi.org\/10.1007\/s00415-026-13997-6","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]},"assertion":[{"value":"25 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors have no conflicts of interest to declare.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The manuscript does not contain clinical studies or patient data.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"480"}}