Potential clinical utility of multiple system atrophy biomarkers

ABSTRACT

Introduction: Multiple system atrophy (MSA), an adult-onset, fatal disorder of uncertain etiology, characterized by parkinsonism, cerebellar, autonomic and motor dysfunctions, is an α-synucleinopathy with glioneuronal degeneration involving multiple parts of the nervous system. The clinical variants correlate with the morphological phenotypes of striatonigral degeneration (MSA-P), olivoponto-cerebellar atrophy (MSA-C), and mixed type MSA. Neuropathological hallmark is the deposition of aberrant α-synuclein in glia and neurons forming cytoplasmic inclusions that cause cell dysfunction/demise.

Areas covered: While our knowledge of the pathogenesis of this proteinopathy is still incomplete, updated consensus criteria and combined biomarkers have increased diagnostic accuracy. Multimodal imaging of structural and functional brain changes gives insight into the pathophysiology and may evaluate disease progression. Currently, the most useful CSF biomarkers are a combination of light chain neurofilament (elevated in MSA), catecholaminergic metabolites, and proteins (α-synuclein, DJ-1, tau). Several blood substances (neurofilament light chain, microRNAs) are non-invasive biomarkers.

Expert commentary: Recent studies suggest that the combination of neuroimaging and fluid biomarkers may be more successful than using single markers to increase the accuracy of the clinical (differential) diagnosis of MSA. Multidisciplinary research to develop more reliable markers for a more exact and early diagnosis and targets for effective treatment are urgently needed.

KEYWORDS:

• Multiple system atrophy
• α-synuclein
• biomarkers
• cerebrospinal fluid
• plasma
• neuroimaging
• diagnostic relevance

Acknowledgment

The author thanks Mr E. Mitter-Ferstl, PhD, for secretarial and graphical work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The study was partially funded by the Society for the Promotion of Research in Experimental Neurology, Vienna, Austria.