Diurnal and Intersubject Variability of Cerebrospinal Fluid Biomarkers in Parkinsonís Disease and Healthy Volunteers
Movement Disorder Society - Dublin, Ireland
Objective: To determine the diurnal fluctuations of specific biomarkers alpha-synuclein, DJ-1, and several amyloid beta species in the cerebrospinal fluid (CSF) of Parkinson's disease (PD) subjects and healthy volunteers and to determine the within-subject and between-subject variability of these markers.
Background: Several biochemical biomarkers are reported to segregate PD from other disorders and may be useful as diagnostic or progression biomarkers. The individual variability of these biomarkers such as alpha-synuclein and DJ-1 is not well understood.
Methods: CSF was collected via a lumbar catheter from thirteen healthy volunteers and 12 PD subjects over 26 hours. CSF alpha-synuclein, DJ-1, hemoglobin, Abeta 1-40 and Abeta 1-42, and total protein levels were measured using ELISA methods to determine the within-subject and between subject variability of these putative biochemical biomarkers.
Results: Concentrations of alpha-synuclein in CSF increased from approximately 800 pg/mL at baseline (0 hours) to approximately 1100 pg/mL (approximately 38%) over 26 hours. ANOVA modeling demonstrated a statistically significant effect of collection time but no change in a two week follow up collection in healthy volunteers. Mean DJ-1 concentrations in CSF did not appear to change over 26 hours. Mean Abeta (1-40 and 1-42) also increased over the collection period in a statistically significant pattern consistent with alpha-synuclein increases. Alpha-synuclein, DJ-1, and Abeta species all correlated with total protein and levels.
Conclusions: Increases in biomarkers such as alpha-synuclein and Abeta species over 26 hours may reflect a gradient effect by frequent CSF sampling at multiple time points over one day. Additionally, it will be important to account for total protein and hemoglobin levels when measuring certain CSF biomarkers. This will be critical to the design of future clinical trials utilizing CSF biomarkers as endpoints.
Authors:†Mark A Frasier, Ken Marek, Peggy Taylor, Chelsea Caspell, Christopher Coffey, Larry Ereshefsky, Mark Yen and Todd Sherer