Multiple System Atrophy Awareness Month and MSA Biomarkers: Wolfgang Singer, MD

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“MSA is a rare disease and is not always on the radar right away when a neurologist sees a patient and having a marker that's easily accessible and easily testable I think will open the path towards an earlier diagnosis. Even if MSA is just suspected, it could be run and ruled out or ruled in, and I think that will hopefully get patients earlier to a diagnosis, earlier into trials, and I think this will really help advance the field going forward.”

In recognition of Multiple System Atrophy (MSA) Awareness Month, NeurologyLive® spoke with Wolfgang Singer, MD, a professor of neurology at Mayo Clinic, about the evolving landscape of biomarker research in MSA—a rare, progressive neurodegenerative disease that presents significant diagnostic challenges because of its clinical overlap with Parkinson disease and other synucleinopathies.

Singer identified α-synuclein seed aggregation assays—including real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA)—as among the most clinically compelling currently. These assays detect pathologic α-synuclein aggregation in cerebrospinal fluid and, more recently, in skin, and have demonstrated the ability to differentiate MSA not only from healthy controls, but also from Parkinson disease and dementia with Lewy bodies. Singer cautioned, however, that assay performance is not uniform across platforms: the MSA signal varies considerably by assay type and run characteristics, and reliable plasma-based assays for diagnostic purposes remain in early development.

Neurofilament light chain was highlighted as an accessible fluid biomarker with demonstrated utility in distinguishing MSA from Parkinson disease and dementia with Lewy bodies in appropriate clinical contexts, though Singer noted it lacks disease specificity as a standalone marker. Phosphorylated α-synuclein detected in cutaneous nerve fibers represents another area of active investigation, with recent data suggesting that deposition patterns by fiber type may enable synucleinopathy subtyping—though Singer noted real-world performance outside controlled trial settings remains under evaluation.

On the imaging front, Singer described meaningful advances in quantitative structural and diffusion MRI targeting regions of known MSA pathology, including the cerebellum and basal ganglia, as well as AI-derived indices that may support both diagnosis and disease progression tracking.

Singer emphasized that earlier and more accessible biomarker-based diagnosis could shorten the diagnostic journey for patients with MSA, facilitate enrollment into clinical trials, and ultimately accelerate therapeutic development in a disease where treatment options remain limited.