PTPR type Q in cerebrospinal fluid reflects ependymal cells dysfunction and is a potential biomarker for adult chronic hydrocephalus
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Background: 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 analysed the feasibility of using CSF PTPRQ concentrations for the additional diagnostic criterion of iNPH in Japanese and Finnish populations.
Methods: We compared PTPRQ concentrations between patients with probable iNPH and neurologically healthy individuals (normal control group [NC]), NPH of acquired and congenital/developmental etiologies, Alzheimer's disease and Parkinson's disease in a Japanese analysis cohort. A corresponding iNPH and NC in 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 NC.
Results: CSF PTPRQ concentrations in the patients with NPH of idiopathic, acquired and congenital/developmental etiologies were significantly higher than those in the NC and with Parkinson's disease, but iNPH showed no significant differences when compared with those having Alzheimer's disease. For the patients with iNPH was detected an area under the receiver operating characteristic curve of 0.860 in the Japanese-iNPH and 0.849 in the Finnish-iNPH group. 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 CSF are related to ependymal dysfunction from ventricular expansion.
Conclusions: CSF PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus.
Keywords: Idiopathic normal pressure hydrocephalus; RNA in situ hybridization; biomarker; cerebrospinal fluid; protein tyrosine phosphatase receptor type Q.