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

PLoS One. 2021 Oct 1;16(10):e0258165. doi: 10.1371/journal.pone.0258165. eCollection 2021.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / genetics
  • Aquaporin 1 / cerebrospinal fluid*
  • Aquaporin 4 / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Diagnosis, Differential*
  • Female
  • Humans
  • Hydrocephalus, Normal Pressure / cerebrospinal fluid
  • Hydrocephalus, Normal Pressure / diagnosis*
  • Hydrocephalus, Normal Pressure / genetics
  • Hydrocephalus, Normal Pressure / pathology
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • tau Proteins / genetics

Substances

  • AQP1 protein, human
  • AQP4 protein, human
  • Amyloid beta-Peptides
  • Aquaporin 4
  • Biomarkers
  • Peptide Fragments
  • tau Proteins
  • Aquaporin 1

Grants and funding

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.