AAN 2026 | Biosignatures to differentiate multiple system atrophy from Parkinson’s disease

So we’ve been very interested in trying to understand ways to differentiate some of these very similar disorders like Parkinson’s disease and multiple system atrophy, which are both characterized by phosphorylated alpha-synuclein. But in the central nervous system, MSA has synuclein within glial cytoplasmic inclusions. But in Parkinson’s disease and dementia with Lewy bodies, they’re seen in Lewy bodies and Lewy neurites, so basically neurons and axons. But we were curious as to whether the peripheral nervous system would give us a window to differentiate between these two disorders. And what we found is, in fact, that we could, if we take skin biopsies and look for phosphorylated alpha-synuclein, patients with MSA have a lot of peripheral synuclein deposition, much more so than Parkinson’s disease. And the deposition is actually within sensory nerve fibers. And so certain areas of the skin, which predominantly are sensory nerves, in contrast, patients with Parkinson’s disease have phosphorylated alpha-synuclein deposited within autonomic nerve fibers, so those around sweat glands or blood vessels or pilomotor muscles. These are the muscles that cause goosebumps. And so these different locations actually really help to separate between the two disorders with very high sensitivity and specificity.

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