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

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 ad...

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Published in:	European journal of neurology Vol. 28; no. 2; pp. 389 - 400
Main Authors:	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., Arai, H.
Format:	Journal Article
Language:	English
Published:	England John Wiley & Sons, Inc 01-02-2021 John Wiley and Sons Inc
Subjects:	Adult Alzheimer Disease Alzheimer's disease Amyloid beta-Peptides Autopsies biomarker Biomarkers Biopsy Cerebrospinal fluid Choroid plexus Congenital diseases Dementia and Cognitive Disorders Diagnostic systems Ependymal cells Humans Hybridization Hydrocephalus Hydrocephalus, Normal Pressure idiopathic normal‐pressure hydrocephalus Movement disorders Neurodegenerative diseases Original Parkinson's disease Phosphatase protein tyrosine phosphatase receptor type Q Protein Tyrosine Phosphatases Protein-tyrosine-phosphatase Proteins Proteomes Receptor-Like Protein Tyrosine Phosphatases, Class 3 Receptors RNA in situ hybridization Tau protein Tyrosine Ventricle RNA in situ hybridization biomarker protein tyrosine phosphatase receptor type Q idiopathic normal-pressure hydrocephalus cerebrospinal fluid
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Summary:	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. Protein tyrosine phosphatase receptor type Q (PTPRQ) extracted from CSF of patients with probable idiopathic normal pressure hydrocephalus (iNPH) by proteome analysis was evaluated as potential biomarker for this condition. Its level from two cohorts ‐ Japanese and Finnish was compared with normal controls and non‐iNPH patients. The levels were significantly lower than non‐iNPH patients, but higher than normal controls. It is highly possible that the elevated PTPRQ levels in CSF are related to ependymal dysfunction from ventricular expansion. CSF PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1351-5101 1468-1331
DOI:	10.1111/ene.14575