title: Oxysterols and Parkinson's disease: evidence that levels of 24S-hydroxycholesterol in cerebrospinal fluid correlates with the duration of the disease.
abstract: Oxysterols are important for cholesterol homeostasis in the brain and may be affected in neurodegenerative diseases. The levels of the brain-derived oxysterol 24S-hydroxycholesterol (24S-OH) have been reported to be markedly reduced in the circulation of patients with Parkinson's disease (PD) (Lee et al., Antioxid. Redox Signal. 11 (2009) 407-420). The finding is surprising in view of the fact that other neurodegenerative diseases are associated with relatively modest effects on the circulating levels of 24S-OH. We determined the plasma and cerebrospinal fluid (CSF) levels of 24S-OH and 27-hydroxycholesterol (27-OH) in patients with PD with different disease duration using a highly accurate method based on isotope dilution-mass spectrometry. All the patients had plasma levels of the different oxysterols within the normal range. When analyzing CSF, 10% of the PD patients were found to have levels of 24S-OH above the cut-off level and interestingly there was a significant correlation between levels of 24S-OH in CSF and duration of the disease (r=0.40, P<0.05). The CSF level of 27-OH was found to be above the cut-off level in 10% of the patients, indicating a defect blood-brain barrier function. There was no correlation between levels of 27-OH in CSF and duration of the disease. These data indicates that oxysterol levels in CSF may be of value to follow disease progression.
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden. Electronic address: ingemar.bjorkhem@karolinska.se.
authors.forename: Ingemar
authors.initials: I
authors.lastname: Björkhem
authors.forename: Anita
authors.initials: A
authors.lastname: Lövgren-Sandblom
authors.forename: Valerio
authors.initials: V
authors.lastname: Leoni
authors.forename: Steve
authors.initials: S
authors.lastname: Meaney
authors.forename: Lovisa
authors.initials: L
authors.lastname: Brodin
authors.forename: Lisette
authors.initials: L
authors.lastname: Salveson
authors.forename: Kristian
authors.initials: K
authors.lastname: Winge
authors.forename: Sven
authors.initials: S
authors.lastname: Pålhagen
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000134:cerebrospinal fluid*; D013997:Time Factors
chemical_list: D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol
keywords: 24S-hydroxycholesterol; 27-Hydroxycholesterol; Biomarkers; Oxysterols