{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:01:25Z","timestamp":1791907285047,"version":"4.3.4"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI16\/00493 and PI19\/01096 t"],"award-info":[{"award-number":["PI16\/00493 and PI19\/01096 t"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Regional Development Fund (FEDER)."},{"name":"Regional Government of Andalusia"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Brain aquaporin 1 (AQP1) and AQP4 are involved in cerebrospinal fluid (CSF) homeostasis and might participate in the origin of hydrocephalus. Studies have shown alterations of perivascular AQP4 expression in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer\u2019s disease (AD). Due to the overlapping of clinical signs between iNPH and certain neurological conditions, mainly AD, specific biomarkers might improve the diagnostic accuracy for iNPH. The goal of the present study was to analyze and quantify the presence of AQP1 and AQP4 in the CSF of patients with iNPH and AD to determine whether these proteins can be used as biomarkers of iNPH. We examined AQP1 and AQP4 protein levels in the CSF of 179 participants (88 women) classified into 5 groups: possible iNPH (81 participants), hydrocephalus associated with other neurological disorders (13 participants), AD (41 participants), non-AD dementia (32 participants) and healthy controls (12 participants). We recorded each participant\u2019s demographic and clinical variables and indicated, when available in the clinical history, the record of cardiovascular and respiratory complications. An ELISA showed virtually no AQP content in the CSF. Information on the vascular risk factors (available for 61 patients) confirmed some type of vascular risk factor in 86% of the patients with possible iNPH and 58% of the patients with AD. In conclusion, the ELISA analysis showed insufficient sensitivity to detect the presence of AQP1 and AQP4 in CSF, ruling out the possible use of these proteins as biomarkers for diagnosing iNPH.<\/jats:p>","DOI":"10.1371\/journal.pone.0258165","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T18:38:57Z","timestamp":1633113537000},"page":"e0258165","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Evaluation of aquaporins in the cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus"],"prefix":"10.1371","volume":"16","author":[{"given":"Laura","family":"Hiraldo-Gonz\u00e1lez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Trillo-Contreras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2588-6904","authenticated-orcid":true,"given":"Pablo","family":"Garc\u00eda-Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Pineda-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reposo","family":"Ram\u00edrez-Lorca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Rodrigo-Herrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena Olivares","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Oliver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bernal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Franco-Mac\u00edas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2131-9013","authenticated-orcid":true,"given":"Javier","family":"Villadiego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4758-9428","authenticated-orcid":true,"given":"Miriam","family":"Echevarr\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"pone.0258165.ref001","article-title":"Prevalence of idiopathic normal pressure hydrocephalus: A prospective, population based study","author":"J Andersson","year":"2019","journal-title":"PLoS ONE"},{"key":"pone.0258165.ref002","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1227\/01.NEU.0000168185.29659.C5","article-title":"Diagnosing idiopathic normal-pressure hydrocephalus","volume":"57","author":"N Relkin","year":"2005","journal-title":"Neurosurgery"},{"key":"pone.0258165.ref003","article-title":"Pathogenesis of idiopathic Normal Pressure Hydrocephalus: A review of knowledge","author":"K Br\u00e4utigam","year":"2019","journal-title":"Journal of Clinical Neuroscience"},{"key":"pone.0258165.ref004","article-title":"Normal pressure hydrocephalus\u2014an overview of pathophysiological mechanisms and diagnostic procedures","author":"P Skalick\u00fd","year":"2020","journal-title":"Neurosurgical Review"},{"key":"pone.0258165.ref005","article-title":"CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics","author":"A Jeppsson","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0258165.ref006","article-title":"Idiopathic normal pressure hydrocephalus has a different cerebrospinal fluid biomarker profile from alzheimer\u2019s disease","author":"N Jingami","year":"2015","journal-title":"J Alzheimer\u2019s Dis."},{"key":"pone.0258165.ref007","article-title":"Normal Pressure Hydrocephalus Associated with Alzheimer\u2019s Disease","author":"K M\u00fcller-Schmitz","year":"2020","journal-title":"Ann Neurol"},{"key":"pone.0258165.ref008","article-title":"Combined effects of aquaporin-4 and hypoxia produce age-related hydrocephalus","author":"JL Trillo-Contreras","year":"2018","journal-title":"Biochim Biophys Acta\u2014Mol Basis Dis"},{"key":"pone.0258165.ref009","article-title":"AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis","author":"J Trillo-Contreras","year":"2019","journal-title":"Cells"},{"key":"pone.0258165.ref010","article-title":"The Glymphatic System and Waste Clearance with Brain Aging: A Review","author":"H Benveniste","year":"2019","journal-title":"Gerontology"},{"key":"pone.0258165.ref011","article-title":"The Glymphatic Pathway: Waste Removal from the CNS via Cerebrospinal Fluid Transport","author":"H Benveniste","year":"2017","journal-title":"Neuroscientist."},{"key":"pone.0258165.ref012","article-title":"Association of perivascular localization of aquaporin-4 with cognition and Alzheimer disease in aging brains","author":"DM Zeppenfeld","year":"2017","journal-title":"JAMA Neurol"},{"key":"pone.0258165.ref013","article-title":"Loss of perivascular aquaporin-4 in idiopathic normal pressure hydrocephalus","author":"MM Hasan-Olive","year":"2019","journal-title":"Glia"},{"key":"pone.0258165.ref014","article-title":"The pathogenesis based on the glymphatic system, diagnosis, and treatment of idiopathic normal pressure hydrocephalus","author":"C Tan","year":"2021","journal-title":"Clinical Interventions in Aging"},{"key":"pone.0258165.ref015","article-title":"Suppression of glymphatic fluid transport in a mouse model of Alzheimer\u2019s disease","author":"W Peng","year":"2016","journal-title":"Neurobiol Dis"},{"key":"pone.0258165.ref016","article-title":"Glymphatic System Impairment in Alzheimer\u2019s Disease and Idiopathic Normal Pressure Hydrocephalus","author":"BC Reeves","year":"2020","journal-title":"Trends in Molecular Medicine"},{"key":"pone.0258165.ref017","article-title":"Glymphatic MRI in idiopathic normal pressure hydrocephalus","author":"G Ringstad","year":"2017","journal-title":"Brain"},{"key":"pone.0258165.ref018","article-title":"A new scale for assessment of severity and outcome in iNPH.","author":"P Hellstr\u00f6m","year":"2012","journal-title":"Acta Neurol Scand"},{"key":"pone.0258165.ref019","article-title":"Diagnosis of idiopathic normal pressure hydrocephalus is supported by MRI-based scheme: A prospective cohort study","author":"M Hashimoto","year":"2010","journal-title":"Cerebrospinal Fluid Res"},{"key":"pone.0258165.ref020","article-title":"The European iNPH Multicentre Study on the predictive values of resistance to CSF outflow and the CSF Tap Test in patients with idiopathic normal pressure hydrocephalus","author":"C Wikkels\u00f8","year":"2013","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0258165.ref021","article-title":"INPH guidelines, part III: The value of supplemental prognostic tests for the preoperative assessment of idiopathic normal-pressure hydrocephalus","author":"A Marmarou","year":"2005","journal-title":"Neurosurgery"},{"key":"pone.0258165.ref022","article-title":"Guidelines for management of idiopathic normal pressure hydrocephalus: Second edition","author":"E Mori","year":"2012","journal-title":"Neurol Med Chir (Tokyo)"},{"key":"pone.0258165.ref023","article-title":"Advancing research diagnostic criteria for Alzheimer\u2019s disease: The IWG-2 criteria","author":"B Dubois","year":"2014","journal-title":"The Lancet Neurology"},{"key":"pone.0258165.ref024","article-title":"An immunoassay that distinguishes real neuromyelitis optica signals from a labeling detected in patients receiving natalizumab","author":"I S\u00e1nchez Gomar","year":"2014","journal-title":"BMC Neurol"},{"key":"pone.0258165.ref025","article-title":"Targeting aquaporin function: Potent inhibition of aquaglyceroporin-3 by a gold-based compound","author":"AP Martins","year":"2012","journal-title":"PLoS One"},{"key":"pone.0258165.ref026","article-title":"Diagnosis and treatment of idiopathic normal pressure hydrocephalus","author":"MA Williams","year":"2016","journal-title":"CONTINUUM Lifelong Learning in Neurology"},{"key":"pone.0258165.ref027","article-title":"Cerebrospinal fluid biomarkers profile of idiopathic normal pressure hydrocephalus","author":"T Schirinzi","year":"2018","journal-title":"Journal of Neural Transmission"},{"key":"pone.0258165.ref028","article-title":"Aquaporins AQP1 and AQP4 in the cerebrospinal fluid of bacterial meningitis patients","author":"J Blocher","year":"2011","journal-title":"Neurosci Lett"},{"key":"pone.0258165.ref029","doi-asserted-by":"crossref","DOI":"10.3233\/JAD-190119","article-title":"Cerebrospinal Fluid Level of Aquaporin4: A New Window on Glymphatic System Involvement in Neurodegenerative Disease?","author":"A Arighi","year":"2019","journal-title":"J Alzheimer\u2019s Dis."},{"key":"pone.0258165.ref030","article-title":"Astrocytic damage is far more severe than demyelination in NMO: A clinical CSF biomarker study","author":"R Takano","year":"2010","journal-title":"Neurology"},{"key":"pone.0258165.ref031","doi-asserted-by":"crossref","first-page":"5810","DOI":"10.3390\/ijms20225810","article-title":"Predictive Value of Serum Antibodies and Point Mutations of AQP4, AQP1 and MOG in A Cohort of Spanish Patients with Neuromyelitis Optica Spectrum Disorders","volume":"20","author":"P Garc\u00eda-Miranda","year":"2019","journal-title":"Int J Mol Sci"},{"key":"pone.0258165.ref032","article-title":"Comparative analysis for the presence of IgG anti-aquaporin-1 in patients with NMO-spectrum disorders","author":"IS Gomar","year":"2016","journal-title":"Int J Mol Sci"},{"key":"pone.0258165.ref033","article-title":"AQP1 overexpression in the CSF of obstructive hydrocephalus and inversion of its polarity in the choroid plexus of a Chiari malformation type II case","author":"L Casta\u00f1eyra-Ruiz","year":"2019","journal-title":"J Neuropathol Exp Neurol"},{"key":"pone.0258165.ref034","article-title":"Cerebrospinal fluid levels of tumor necrosis factor alpha and aquaporin 1 in patients with mild cognitive impairment and idiopathic normal pressure hydrocephalus","author":"L Casta\u00f1eyra-Ruiz","year":"2016","journal-title":"Clin Neurol Neurosurg."},{"key":"pone.0258165.ref035","article-title":"Astrogliosis and impaired aquaporin-4 and dystrophin systems in idiopathic normal pressure hydrocephalus","author":"PK Eide","year":"2018","journal-title":"Neuropathol Appl Neurobiol"},{"key":"pone.0258165.ref036","article-title":"Neuromyelitis optica spectrum disorder with increased aquaporin-4 microparticles prior to autoantibodies in cerebrospinal fluid: A case report","author":"S Bejerot","year":"2019","journal-title":"J Med Case Rep."},{"key":"pone.0258165.ref037","article-title":"Hydrocephalus and aquaporins: Lessons learned from the bench","author":"AS Filippidis","year":"2011","journal-title":"Child\u2019s Nervous System."},{"key":"pone.0258165.ref038","article-title":"Idiopathic normal pressure hydrocephalus: Thoughts on etiology and pathophysiology.","author":"H. Chrysikopoulos","year":"2009","journal-title":"Med Hypotheses"},{"key":"pone.0258165.ref039","article-title":"Vascular risk factors in INPH: A prospective case-control study (the INPH-CRasH study).","author":"H Israelsson","year":"2017","journal-title":"Neurology"},{"key":"pone.0258165.ref040","article-title":"Sleep-Disordered Breathing and Idiopathic Normal-Pressure Hydrocephalus: Recent Pathophysiological Advances","author":"GC Rom\u00e1n","year":"2019","journal-title":"Current Neurology and Neuroscience Reports"},{"key":"pone.0258165.ref041","article-title":"Increased prevalence of cardiovascular disease in idiopathic normal pressure hydrocephalus patients compared to a population-based cohort from the HUNT3 survey","author":"PK Eide","year":"2014","journal-title":"Fluids Barriers CNS"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258165","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T18:39:27Z","timestamp":1633113567000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258165"}},"subtitle":[],"editor":[{"given":"Michael C.","family":"Burger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0258165","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,1]]}}}