{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:01:23Z","timestamp":1791907283081,"version":"4.3.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Umea University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Fluids Barriers CNS"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aquaporin-4 (AQP4) is crucial for brain fluid regulation and glymphatic system function. Idiopathic normal pressure hydrocephalus (INPH) is characterized by impaired CSF flow and is treated with shunt surgery. This study investigated AQP4 levels in INPH patients to explore its role in pathophysiology and as a potential biomarker for shunt response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CSF samples from 233 INPH patients and 29 controls were analysed. AQP4 levels were compared between preoperative patients and controls, before and after shunt surgery (110 patients), and between shunt responders and non-responders (204 patients). A bead-based assay was used to measure AQP4, and outcomes were assessed by postoperative changes in maximum gait velocity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In unadjusted analyses, preoperative AQP4 levels were lower in INPH patients than in controls; however, this difference did not remain after adjustment for pre-analytical and demographic confounders (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.87). Postoperative AQP4 levels were higher (median 1646 AU IQR 1347\u20131976) than preoperative levels (1166 AU IQR: 976\u20131345;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and the magnitude of increase showed a modest correlation with gait improvement (r\u209b = 0.22,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.022). Shunt responders had lower preoperative AQP4 levels median 1089 AU, IQR 971\u20131277) than non-responders (median 1213 AU, IQR 1074\u20131361;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008). Pre-analytical factors, including storage duration and sample processing, were strong determinants of measured AQP4 levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CSF AQP4 levels in INPH did not differ from those in controls and were highly sensitive to pre-analytical sample handling. CSF AQP4 levels increased following shunt surgery. A potential prognostic value of CSF AQP4 is suggested but requires further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12987-026-00809-2","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T12:48:39Z","timestamp":1776775719000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["CSF Aquaporin-4 levels in controls and in idiopathic normal pressure hydrocephalus before and after shunt surgery"],"prefix":"10.1186","volume":"23","author":[{"given":"Johan Eriksson","family":"De Ryst","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Bergstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Mravinacova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"B\u00e4ckstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Qvarlander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"M\u00e5nberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Eklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Malm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"issue":"6","key":"809_CR1","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41583-021-00454-8","volume":"22","author":"N MacAulay","year":"2021","unstructured":"MacAulay N. Molecular mechanisms of brain water transport. Nat Rev Neurosci. 2021;22(6):326\u201344.","journal-title":"Nat Rev Neurosci"},{"issue":"147","key":"809_CR2","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. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med. 2012;4(147):147ra11.","journal-title":"Sci Transl Med"},{"key":"809_CR3","doi-asserted-by":"crossref","unstructured":"Mestre H, Hablitz LM, Xavier AL, Feng W, Zou W, Pu T et al. Aquaporin-4-dependent glymphatic solute transport in the rodent brain. Elife. 2018;7.","DOI":"10.7554\/eLife.40070"},{"issue":"9","key":"809_CR4","doi-asserted-by":"publisher","first-page":"104987","DOI":"10.1016\/j.isci.2022.104987","volume":"25","author":"T Bohr","year":"2022","unstructured":"Bohr T, Hjorth PG, Holst SC, Hrabetova S, Kiviniemi V, Lilius T, et al. The glymphatic system: current understanding and modeling. iScience. 2022;25(9):104987.","journal-title":"iScience"},{"issue":"5","key":"809_CR5","doi-asserted-by":"publisher","first-page":"e0217705","DOI":"10.1371\/journal.pone.0217705","volume":"14","author":"J Andersson","year":"2019","unstructured":"Andersson J, Rosell M, Kockum K, Lilja-Lund O, Soderstrom L, Laurell K. Prevalence of idiopathic normal pressure hydrocephalus: a prospective, population-based study. 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Comparison of the CSF dynamics between patients with idiopathic normal pressure hydrocephalus and healthy volunteers. J Neurosurg. 2018:1\u20136."},{"issue":"3","key":"809_CR9","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1227\/neu.0000000000002225","volume":"92","author":"M Luciano","year":"2023","unstructured":"Luciano M, Holubkov R, Williams MA, Malm J, Nagel S, Moghekar A, et al. Placebo-controlled effectiveness of idiopathic normal pressure hydrocephalus shunting: a randomized pilot trial. Neurosurgery. 2023;92(3):481\u20139.","journal-title":"Neurosurgery"},{"issue":"3","key":"809_CR10","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.molmed.2019.11.008","volume":"26","author":"BC Reeves","year":"2020","unstructured":"Reeves BC, Karimy JK, Kundishora AJ, Mestre H, Cerci HM, Matouk C, et al. Glymphatic system impairment in Alzheimer\u2019s Disease and idiopathic normal pressure hydrocephalus. 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J Cereb Blood Flow Metab. 2019;39(7):1355\u201368.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"809_CR13","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1001\/jamaneurol.2016.4370","volume":"74","author":"DM Zeppenfeld","year":"2017","unstructured":"Zeppenfeld DM, Simon M, Haswell JD, D\u2019Abreo D, Murchison C, Quinn JF, et al. Association of perivascular localization of Aquaporin-4 with cognition and Alzheimer Disease in aging brains. JAMA Neurol. 2017;74(1):91\u20139.","journal-title":"JAMA Neurol"},{"issue":"5","key":"809_CR14","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1111\/nan.12420","volume":"44","author":"PK Eide","year":"2018","unstructured":"Eide PK, Hansson HA. Astrogliosis and impaired Aquaporin-4 and dystrophin systems in idiopathic normal pressure hydrocephalus. 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Biochim Biophys Acta Mol Basis Dis. 2018;1864(10):3515\u201326.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"3","key":"809_CR21","doi-asserted-by":"publisher","first-page":"663","DOI":"10.3233\/JAD-190119","volume":"69","author":"A Arighi","year":"2019","unstructured":"Arighi A, Di Cristofori A, Fenoglio C, Borsa S, D\u2019Anca M, Fumagalli GG, et al. Cerebrospinal fluid level of Aquaporin4: a new window on glymphatic system involvement in neurodegenerative disease? J Alzheimers Dis. 2019;69(3):663\u20139.","journal-title":"J Alzheimers Dis"},{"issue":"10","key":"809_CR22","doi-asserted-by":"publisher","first-page":"e0258165","DOI":"10.1371\/journal.pone.0258165","volume":"16","author":"L Hiraldo-Gonzalez","year":"2021","unstructured":"Hiraldo-Gonzalez L, Trillo-Contreras JL, Garcia-Miranda P, Pineda-Sanchez R, Ramirez-Lorca R, Rodrigo-Herrero S, et al. Evaluation of aquaporins in the cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus. 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This study was performed in accordance with the guidelines of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All patients provided written consent to save CSF for future research purposes at the time of lumbar puncture. Participants in this study were informed about the study via a letter, which included an option to opt out if they did not wish to participate. Individuals deceased at the time inclusion began (2020) were automatically incorporated in the cohort.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"62"}}