Objective: To evaluate a comprehensive panel of cerebral spinal fluid (CSF) markers in multiple system atrophy (MSA) to define those with potential as future disease biomarkers.

Background: The diagnosis of MSA is currently mainly based on clinical consensus criteria which capture the disease at a late stage as indicated by the short median survival from diagnosis of only 1.8 years. The utilization of autonomic biomarkers allows for diagnosis at an earlier but still relatively advanced stage. Diagnosis at a yet earlier clinical, or even preclinical stage would have significant implications, not only in light of emerging potential disease-modifying therapies. Several novel CSF biomarkers for MSA have recently surfaced in the literature.

Methods: CSF was collected in 24 well-characterized patients with early MSA (UMSARS I score ≤18) and 14 sex- and age-matched healthy controls. A panel of potential MSA biomarkers was analyzed using dedicated ELISA and HPLC assays to include markers of central axonal degeneration (neurofilament light chain, NFL), central dopaminergic and noradrenergic neuronal function (L-DOPA, 3,4-dihydroxyphenylacetic acid [DOPAC], norepinephrine [NE], dihydroxyphenylglycol [DHPG], and other catechols), α-synuclein (Asyn, as total, phosphorylated, and oligomeric form), as well as various cytokines including IL-6 and Flt-3 ligand.

Results: NFL was markedly increased in MSA providing perfect separation from controls (4880±1711 vs 900±262 ng/ml, p<0.0001). Other markers with significant group differences between patients and controls included DOPAC (157±70 vs 283±103pg/ml, p<0.001) and other catechols (including NE, DHPG, and L-DOPA), which were all significantly decreased in MSA. Total Asyn was also lower in MSA than controls (0.077±0.050 vs 0.178±0.105ng/ml, p=0.02), but neither Asyn oligomers nor phosphorylated Asyn differed between groups. None of the tested cytokines were significantly different between groups.

Conclusions: A comprehensive panel of CSF markers found NFL, several catechols (DOPAC, NE, DHPG, L-DOPA), and total Asyn to have biomarker potential for MSA. Studies are now ongoing to expand these pilot data, contrast the findings to other synucleinopathies, and explore the value of a combination of these markers as MSA CSF panel.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/spinal-fluid-biomarkers-for-multiple-system-atrophy-a-pilot-study/