December 9, 2025

@michaelokun

Can we crack Parkinson’s subtypes from a simple skin sample/biopsy? Alpha synuclein is a protein that misfolds and aggregates in Parkinson’s and can be detected in tissues like your skin through the use of amplification assays. Magdalena Vieregge and colleagues describe in a new paper in the European Journal of Neurology how dermal seed amplification assays may help us to understand Parkinson’s subtypes. The authors address the challenges in developing this technology, especially in real-world cohorts. Key Points: - Higher titers showed up in idiopathic REM Sleep Behavior Disorder (iRBD) and pointed to stronger early alpha synuclein activity in the peripheral nerves in a defined pre-motor PD group. - Subtype differences were small, as widespread nerve involvement in later stages could be blurring distinctions. - Quantitative SAA measures seemed to vary perhaps because amplification reactions are known to be nonlinear and seem to be sensitive to small experimental changes. My take: Parkinson’s is not just a disease of the brain. It is a whole-body disease, and researchers have recently been keying in on changes present in the skin. This article included 5 points that resonated w/ me: 1- Skin may offer us clues about early Parkinson’s pathways, however once PD is established, the signal seems to become less distinct. 2- iRBD carries a strong biological footprint, suggesting early and heavy involvement of peripheral nerves. 3- Folks should know that alpha synuclein can spread widely. The wide spread makes subtype sorting tricky, especially w/in clinic settings. 4- Many SAA tools frequently show promise, and we will need standardization to make them reliable across centers. 5- Better understanding of early nerve involvement may someday help us intervene earlier in PD. https://onlinelibrary.wiley.com/doi/10.1111/ene.70453 #michaelokun #parkinson #fixelinstitute