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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

                Journal
                PLoS One
                PloS one
                Public Library of Science (PLoS)
                1932-6203
                1932-6203
                2021
                : 16
                : 10
                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.
                Article
                PONE-D-21-19251
                10.1371/journal.pone.0258165
                8486078
                34597351
                7f6e944d-4505-4a3e-a657-ee6539e74d60
                History

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