November 14, 2025

@michaelokun

Can the biomarker of alpha synuclein seed amplification really track Parkinson's disease progression? Spoiler alert: The approach cannot serve as a stand alone speedometer for day to day symptom progression. A seed amplification assay is a lab technique where tiny clumps of misfolded alpha synuclein are exposed to the right conditions to copy themselves many times, so that even very small amounts become detectable. Belete and colleagues describe in a new paper in Movement Disorders Clinical Practice how alpha synuclein seed amplification behaves over five years in Parkinson's and whether it can serve as a marker of disease progression. Key Points: - Baseline alpha synuclein seed amplification kinetic measures did not meaningfully improve prediction of five year changes in motor scores, thinking scores or levodopa dose in folks w/ early sporadic Parkinson's. - Faster alpha synuclein seeding at baseline was linked w/ higher scores on a key question about dream enactment behavior over five years, suggesting a possible connection to sleep related non motor features. - Different seed amplification protocols on the same spinal fluid sample revealed different kinetic profiles. - Serum neurofilament light levels added little for predicting motor progression. My take: Detecting disease progression is and will be a challenge in Parkinson's. We will likely need to combine many measures inclusive of imaging. Here are 5 points that really resonated w/ me: 1- Alpha synuclein seed amplification is already a powerful test for detecting PD biology, however this study suggests it is not yet ready to serve as a stand alone speedometer for day to day symptom progression. 2- For movement, thinking and medication needs over five years, traditional clinical exams told more of the story than the synuclein seeding. 3- Faster seeding profiles linked w/ more dream enactment symptoms, which hints that these tests may someday help health care providers flag who is at higher risk for certain sleep problems. 4- Different lab recipes for seed amplification gave different kinetic readouts. 5- a combination approach of tests may be the answer. #fixelinstitute #michaelokun #parkinson