Presenter of 1 Presentation
TARGETING REACTIVE ASTROCYTOSIS FOR NOVEL BIOMARKERS OF DISEASE SEVERITY IN MULTIPLE SYSTEM ATROPHY
Abstract
Aims
Multiple System Atrophy (MSA) is a rapidly progressive neurodegenerative disease with a profound neuroinflammatory component. We hypothesized that reactive astrocytosis as part of MSA-related neuroinflammation is a suitable target for biomarker development and set out to evaluate glial fibrillary acidic protein (GFAP) in plasma and CSF of MSA patients. We further explored [18F]D2-Deprenyl-PET imaging in MSA patients, a novel PET-Imaging method targeting MAO-B upregulation, as additional correlate of reactive astrocytosis.
Methods
We analyzed 23 plasma samples (8 MSA-P, 15 MSA-C) and 12 CSF samples (4 MSA-P, 8 MSA-C) using the Simoa® Quanterix Platform. GFAP values were correlated with baseline UMSARS and MoCA scores and longitudinal increase in UMSARS values. In 11 patients, we additionally performed [18F]D2-Deprenyl-PET imaging (4 MSA-P, 7 MSA-C) and correlated results with fluid biomarkers.
Results
Both, plasma and CSF levels of GFAP showed significant positive correlation with baseline UMSARS values (p < 0.05) and negative correlation with MoCA scores (p < 0.05). There was no correlation of either plasma or CSF GFAP values with longitudinal increase in UMSARS values. In first [18F]D2-Deprenyl-PETs, we detected phenotype-specific differences in standardized uptake value ratios (SUVr), with MSA-P showing higher putaminal and MSA-C showing higher cerebellar tracer binding.
Conclusions
This data indicate that both plasma and CSF based GFAP values might be suitable fluid-based biomarkers for disease severity in MSA. Preliminary [18F]D2-Deprenyl-PET results indicate the potential to detect phenotype-specific regional differences of reactive astrocytosis in MSA and highlight the importance of neuroinflammation for the pathological disease process in MSA.