CSF Biomarkers in Spinocerebellar Ataxias (P05.018)

Abstract

Objective: To identify potential biomarkers in the cerebrospinal fluid (CSF) of patients with spinocerebellar ataxia (SCA) 1, SCA2, SCA6, and multiple system atrophy of the cerebellar type (MSA-C). Background Levels of proteins such as α-synuclein, tau, and DJ-1 have shown promise as potential type-specific and stage-specific bioimarkers of several neurodegenerative diseases, including Parkinson9s, Alzheimer9s, multiple sclerosis, and ALS. DJ-1 has recently been shown to be involved in oxidative stress and to be elevated in the early stages of Parkinson9s. α-synuclein is thought to be involved in vesicle trafficking and is decreased in the CSF of Parkinson9s patients. Tau is a general marker of neuroaxonal damage elevated in Alzheimer9s, ALS, and multiple sclerosis. Limited to no biomarker data has been previously published in regards to ataxia disorders. Design/Methods: The CSF samples were obtained for this study from 26 patients: 5 diagnosed with SCA1, 6 with SCA2, 5 with SCA6, 5 with MSA-C, and 5 controls with no neurological pathology. CSF was analyzed using commercial enzyme-linked immunoabsorption assays (ELISAs) to determine protein concentrations of α-synuclein, tau, and DJ-1. Statistical analysis was performed using a Mann-Whitney U nonparametric test with appropriate post-hoc Bonferroni corrections. Results: DJ-1 levels were unchanged in all the disease states. Levels of α-synuclein were elevated only in SCA-2 patients (p=0.004) at 0.6965 ng/mL vs. 0.4312 ng/mL in controls. Tau protein was elevated in both MSA-C (p=0.004) and SCA2 (p=0.002) patients at 76.117 pg/mL and 106.634 pg/mL respectively as compared to 44.154 pg/mL in the controls. Conclusions: Elevated levels of both tau and α-synuclein in SCA2 and none of the other SCAs examined indicate a possible differentiation between diseases that present in a clinically similar manner. Additionally, as very little is known about MSA-C, elevated levels of tau could provide insight into pathogenesis. Supported by: National Ataxia Foundation, JayD Schlueter Fund. Disclosure: Dr. Brouillette has nothing to disclose. Dr. Gomez has nothing to disclose.