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      Evaluation of aquaporins in the cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus

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          Abstract

          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’s 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’s 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.

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          Most cited references41

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          Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria.

          In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Glymphatic MRI in idiopathic normal pressure hydrocephalus

            The glymphatic system has been shown in animal studies to support the clearance of waste metabolites from the brain interstitial space. Using MRI, Ringstad et al. visualize the glymphatic system for the first time in humans. Glymphatic clearance is sleep-dependent and is impaired in patients with normal pressure hydrocephalus.
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              Diagnosing idiopathic normal-pressure hydrocephalus.

              The precise incidence and prevalence of idiopathic normal-pressure hydrocephalus (INPH) is not known, and evidence-based clinical diagnostic criteria have not been developed previously. This report contains evidence-based guidelines for clinical diagnosis of INPH that are intended to facilitate future epidemiological studies of INPH, promote earlier and more accurate diagnosis, and ultimately improve treatment outcome. The criteria for the diagnosis of INPH are based on evidence from the medical literature, supplemented as necessary by expert opinion. From 1966 to 2003, 653 publications on "normal-pressure hydrocephalus" were cited in MEDLINE, including 29 articles that met the more stringent criteria of including "idiopathic normal-pressure hydrocephalus" in their title. Additional studies were considered that explicitly identified INPH cases and/or specified the criteria for a diagnosis of INPH. Studies were graded according to the class of evidence and results summarized in evidentiary tables. For issues of clinical relevance that lacked substantive evidence from the medical literature, the opinions of consulting experts were considered and contributed to "Options." Evidence-based guidelines for the clinical diagnosis of INPH have been developed. A detailed understanding of the range of clinical manifestations of this disorder and adherence to practice guidelines should improve the timely and accurate recognition of this disorder. It is recommended that INPH be classified into probable, possible, and unlikely categories. We hope that these criteria will be widely applied in clinical practice and will promote greater consistency in patient selection in future clinical investigations involving INPH.
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                Author and article information

                Contributors
                Role: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: InvestigationRole: MethodologyRole: Resources
                Role: InvestigationRole: MethodologyRole: Supervision
                Role: InvestigationRole: Resources
                Role: InvestigationRole: Resources
                Role: ResourcesRole: Supervision
                Role: MethodologyRole: Resources
                Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: Supervision
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: Formal analysisRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 October 2021
                2021
                : 16
                : 10
                : e0258165
                Affiliations
                [1 ] Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, (HUVR)/Spanish National Research Council (CSIC)/University of Seville, Seville, Spain
                [2 ] Department of Physiology and Biophysics, University of Seville, Seville, Spain
                [3 ] Clinical Neuroscience Management Unit, Neurology Service, University Hospital Virgen del Rocío, Seville, Spain
                [4 ] Clinical Neuroscience Management Unit, Neurosurgery Service, University Hospital Virgen del Rocío, Seville, Spain
                [5 ] Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Seville, Spain
                Goethe University Hospital Frankfurt, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-2588-6904
                https://orcid.org/0000-0003-2131-9013
                https://orcid.org/0000-0002-4758-9428
                Article
                PONE-D-21-19251
                10.1371/journal.pone.0258165
                8486078
                34597351
                7f6e944d-4505-4a3e-a657-ee6539e74d60
                © 2021 Hiraldo-González et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 June 2021
                : 21 September 2021
                Page count
                Figures: 2, Tables: 2, Pages: 12
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: PI16/00493 and PI19/01096 t
                Award Recipient :
                Funded by: European Regional Development Fund (FEDER).
                Award Recipient :
                Funded by: Regional Government of Andalusia
                Award Recipient :
                This research was funded by grants PI16/00493 and PI19/01096 to M.E. from the Spanish Ministry of Economy and Competitiveness, co-financed by the Carlos III Health Institute (ISCIII) and European Regional Development Fund (FEDER). J.L.T-C. was partially supported by the Regional Government of Andalusia and FEDER funds through a program for recruitment of young researchers.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Cerebrospinal Fluid
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Cerebrospinal Fluid
                Biology and Life Sciences
                Physiology
                Body Fluids
                Cerebrospinal Fluid
                Biology and Life Sciences
                Anatomy
                Nervous System
                Cerebrospinal Fluid
                Medicine and Health Sciences
                Anatomy
                Nervous System
                Cerebrospinal Fluid
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Dementia
                Alzheimer's Disease
                Medicine and Health Sciences
                Neurology
                Dementia
                Alzheimer's Disease
                Medicine and Health Sciences
                Medical Conditions
                Neurodegenerative Diseases
                Alzheimer's Disease
                Medicine and Health Sciences
                Neurology
                Neurodegenerative Diseases
                Alzheimer's Disease
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Medicine and Health Sciences
                Neurology
                Hydrocephalus
                Medicine and Health Sciences
                Diagnostic Medicine
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                Medicine and Health Sciences
                Neurology
                Medicine and Health Sciences
                Medical Conditions
                Cardiovascular Diseases
                Cardiovascular Disease Risk
                Medicine and Health Sciences
                Cardiology
                Cardiovascular Medicine
                Cardiovascular Diseases
                Cardiovascular Disease Risk
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