Age-related increase of prostaglandin D₂ synthase concentration and glycation in ovine cerebrospinal fluid

Prostaglandin D₂ synthase (PGDS) is a glycoprotein that is exclusively brain derived and is one of the most abundant proteins in the cerebrospinal fluid (CSF). Due to its high CSF specificity, it can be used as a tool for the diagnosis of central nervous system (CNS) disorders. However, several studies have yielded contradictory CSF PGDS concentrations in various CNS neurodegenerative disorders. Sheep CSF samples from different ages were used in this study and 2-dimensional electrophoresis (2-DE) was applied in PGDS identification and concentration calculation. SYPRO Ruby Protein Gel Stain was the staining method used to stain the 2-DE gel protein spots. Pro-Q Emerald 488 Staining for Glycoproteins was used for the staining of glycoproteins. A total of nine PGDS isoforms were identified and CSF total PGDS concentration was calculated to increase linearly by 44% from young (0.9323 ± 0.0637 mg dL^-1) to old (1.3669 ± 0.0558 mg dL^-1). However, the proportion of CSF total PGDS as a percentage of CSF total protein was discovered to decrease exponentially with age. This was due to the influence of larger age-related increase in CSF albumin concentration (>200% from young to old) as albumin is the most abundant protein in the CSF (>60% of total CSF proteins). Active deglycosylation was not observed in PGDS isoforms during healthy ageing. Some PGDS isoforms were observed to have age-related increase in glycation. These findings suggest that CSF PGDS concentration is increased during healthy ageing and must be taken into consideration when using PGDS as a potential biomarker in diagnosing CNS neurodegenerative disorders. Whether age-related increase in the glycation of some CSF PGDS isoforms will result in detrimental effects on the PGDS protein function needs further investigations.