Cutaneous α-Synuclein Signatures in Patients With Multiple System Atrophy and Parkinson Disease, 2023, Gibbons et al

Title: Cutaneous α-Synuclein Signatures in Patients With Multiple System Atrophy and Parkinson Disease

Authors: Christopher Gibbons, Ningshan Wang 1, Sharika Rajan 1, Drew Kern 1, Jose-Alberto Palma 1, Horacio Kaufmann 1, Roy Freeman 2

Abstract:

Background and objectives: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder caused by the abnormal accumulation of α-synuclein in the nervous system. Clinical features include autonomic and motor dysfunction, which overlap with those of Parkinson disease (PD), particularly at early disease stages. There is an unmet need for accurate diagnostic and prognostic biomarkers for MSA and, specifically, a critical need to distinguish MSA from other synucleinopathies, particularly PD. The purpose of the study was to develop a unique cutaneous pathologic signature of phosphorylated α-synuclein that could distinguish patients with MSA from patients with PD and healthy controls.

Methods: We studied 31 patients with MSA and 54 patients with PD diagnosed according to current clinical consensus criteria. We also included 24 matched controls. All participants underwent neurologic examinations, autonomic testing, and skin biopsies at 3 locations. The density of intraepidermal, sudomotor, and pilomotor nerve fibers was measured. The deposition of phosphorylated α-synuclein was quantified. Results were compared with clinical rating assessments and autonomic function test results.

Results: Patients with PD had reduced nerve fiber densities compared with patients with MSA (p < 0.05, all fiber types). All patients with MSA and 51/54 with PD had evidence of phosphorylated α-synuclein in at least one skin biopsy. No phosphorylated α-synuclein was detected in controls. Patients with MSA had greater phosphorylated α-synuclein deposition (p < 0.0001) and more widespread peripheral distribution (p < 0.0001) than patients with PD. These results provided >90% sensitivity and specificity in distinguishing between the 2 disorders.

Discussion: α-synuclein is present in the peripheral autonomic nerves of patients with MSA and when combined with synuclein distribution accurately distinguishes MSA from PD.

Classification of evidence: This study provides Class II evidence that measurement of phosphorylated α-synuclein in skin biopsies can differentiate patients with MSA from those with PD.

© 2023 American Academy of Neurology.

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Link: https://pubmed.ncbi.nlm.nih.gov/36657992/

 

Hello all, this study came onto my radar after reading the following media article on the search for a biomarker and treatments for Long Covid, published yesterday:

Long COVID is devastating and far from rare. As infections rise again, why are we still ignoring it? | Salon.com

In the media article, the journalist states:

• "a new skin test has proven effective at detecting alpha-synuclein clumps (the misfolded proteins in the nervous system that indicate a disorder), thereby providing a means of clinically diagnosing synucleinopathies like Parkinson's at far earlier stages. This needs the full weight of funding behind it, with the aim of rolling out these skin biopsies on long COVID patients. If atypical alpha-synuclein is detected across long COVID patients, it'd be convincing evidence that the condition is the beginning of a developing neurodegenerative disease. This could be a real game changer".

The journalist is referring here to the skin biopsy results published in the April 2023 study outlined in the first post in this thread, published in the journal Neurology (American Academy of Neurology). The purpose of that study was to "develop a unique cutaneous pathologic signature of phosphorylated α-synuclein that could distinguish patients with MSA from patients with PD and healthy controls." I note that the study authors are founders of a US company, CND Life Sciences (CND Life Sciences - Home of the Syn-One Test®) which has been backed by NIH grants and markets itself as "[bringing] the first commercially available skin-based test [the Syn-One Test®] to help clinicians diagnose Parkinson’s disease and related disorders". The study should be viewed in this light.

My question is: does anyone know whether any researchers in the field of ME/CFS or Long Covid have yet tried to replicate/expand this study by including ME/CFS and Long COVID patient cohorts alongside PD, MSA and healthy control cohorts to see if the this novel skin biopsy test (Syn-One Test®) can distinguish all groups? At face value - though independent replication/corroboration will of course be required - the fact that 82 out of 85 MSA/PD patients reportedly showed evidence of phosphorylated α-synuclein in at least one skin biopsy in the above study, whereas no healthy controls did, seems compelling to me. I am no expert in this area however.

All thoughts - especially healthy skepticism - welcome!

Ps. This is the first research study I've posted on the forum - apologies if I've got the format wrong or replicated earlier threads, moderators please feel free to put me right. Thanks!

 

Thanks Hutan for these v helpful pointers.