Protein tyrosine phosphatase receptor type Q in cerebrospinal fluid reflects ependymal cell dysfunction and is a potential biomarker for adult chronic hydrocephalus. (1st November 2020)

• Record Type: Journal Article
• 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.
• Is Part Of: European journal of neurology. Volume 28:Number 2(2021)
• Page Start: 389
• Page End: 400
• Publication Date: 2020-11-01
• Subjects: biomarker -- cerebrospinal fluid -- idiopathic normal‐pressure hydrocephalus -- protein tyrosine phosphatase receptor type Q -- RNA in situ hybridization; Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.14575
• Languages: English
• ISSNs: 1351-5101

Abstract

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. Abstract : 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.