University of Oulu

Nakajima, M., Rauramaa, T., Mäkinen, P.M., Hiltunen, M., Herukka, S.‐K., Kokki, M., Musialowicz, T., Jyrkkänen, H.‐K., Danner, N., Junkkari, A., Koivisto, A.M., Jääskeläinen, J.E., Miyajima, M., Ogino, I., Furuta, A., Akiba, C., Kawamura, K., Kamohara, C., Sugano, H., Tange, Y., Karagiozov, K., Leinonen, V. and Arai, H. (2021), Protein tyrosine phosphatase receptor type Q in cerebrospinal fluid reflects ependymal cell dysfunction and is a potential biomarker for adult chronic hydrocephalus. Eur J Neurol, 28: 389-400. https://doi.org/10.1111/ene.14575

Protein tyrosine phosphatase receptor type Q in cerebrospinal fluid reflects ependymal cell dysfunction and is a potential biomarker for adult chronic hydrocephalus

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Author: Nakajima, M.1; Rauramaa, T.2,3; Mäkinen, P. M.4;
Organizations: 1Department of Neurosurgery, Juntendo University Faculty of Medicine, Tokyo, Japan
2Institute of Clinical Medicine-Pathology, University of Eastern, Finland
3Department of Pathology, Kuopio University Hospital, Kuopio, Finland
4Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
5Institute of Clinical Medicine – Neurology, University of Eastern Finland, Kuopio, Finland
6Neurocentre, Neurology, Kuopio University Hospital, Kuopio, Finland
7Department of Anaesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland
8Institute of Clinical Medicine-Neurosurgery, University of Eastern, Finland
9Neurocentre, Neurosurgery, Kuopio University Hospital, Kuopio, Finland
10Department of Psychiatry and Behavioural Science, Juntendo University Faculty of Medicine, Tokyo, Japan
11Unit of Clinical Neuroscience, Neurosurgery, University of Oulu and Medical Research Centre, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202102235752
Language: English
Published: John Wiley & Sons, 2020
Publish Date: 2021-02-23
Description:

Abstract

Background and purpose: Protein tyrosine phosphatase receptor type Q (PTPRQ) was extracted from the cerebrospinal fluid (CSF) of patients with probable idiopathic normal‐pressure hydrocephalus (iNPH) by proteome analysis. We aimed to assess the feasibility of using CSF PTPRQ concentrations for the additional diagnostic criterion of iNPH in Japanese and Finnish populations.

Methods: We compared PTPRQ concentrations among patients with probable iNPH and neurologically healthy individuals (normal control [NC] group), patients with normal‐pressure hydrocephalus (NPH) of acquired and congenital/developmental aetiologies, patients with Alzheimer’s disease and patients with Parkinson’s disease in a Japanese analysis cohort. A corresponding iNPH group and NC group in a Finnish cohort was used for validation. Patients in the Finnish cohort who underwent biopsy were classified into two groups based on amyloid and/or tau deposition. We measured PTPRQ expression levels in autopsied brain specimens of iNPH patients and the NC group.

Results: Cerebrospinal fluid PTPRQ concentrations in the patients with NPH of idiopathic, acquired and congenital/developmental aetiologies were significantly higher than those in the NC group and those with Parkinson’s disease, but iNPH showed no significant differences when compared with those in the Alzheimer’s disease group. For the patients with iNPH, the area under the receiver‐operating characteristic curve was 0.860 in the Japanese iNPH and 0.849 in the Finnish iNPH cohorts. Immunostaining and in situ hybridization revealed PTPRQ expression in the ependymal cells and choroid plexus. It is highly possible that the elevated PTPRQ levels in the CSF are related to ependymal dysfunction from ventricular expansion.

Conclusions: Cerebrospinal fluid PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus.

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Series: European journal of neurology
ISSN: 1351-5101
ISSN-E: 1468-1331
ISSN-L: 1351-5101
Volume: 28
Issue: 2
Pages: 389 - 400
DOI: 10.1111/ene.14575
OADOI: https://oadoi.org/10.1111/ene.14575
Type of Publication: A1 Journal article – refereed
Field of Science: 3112 Neurosciences
Subjects:
Funding: The Graduate School Research Programme of Juntendo University and the Juntendo University Research Institute for Diseases of Old Age (Tokyo, Japan) supported the present study. This work was supported in part by the Private University Research Branding Project by the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare of Japan [2017‐Nanchi‐General‐037] and Grants‐in‐Aid for Scientific Research [grant numbers 16KK0187, 17K10908, 18H02916, 20K09398] from the Japan Society for the Promotion of Science. This work was also supported by the Academy of Finland [grant number 307866]; EVO/VTR [grant number 5053149] of Kuopio University Hospital, Sigrid Juselius Foundation; the Strategic Funding of the University of Eastern Finland (UEF‐Brain), FP7, Grant Agreement [grant number 601055]; and VPH Dementia Research Enabled by IT VPH‐DARE@IT and BIOMARKAPD project in the JPND Programme.
Copyright information: © 2020 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
  https://creativecommons.org/licenses/by-nc/4.0/