α-Synuclein Seed Amplification Assay Classifies Parkinson Disease

High sensitivity and specificity seen for Parkinson disease; α-synuclein SAA can also detect prodromal individuals
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Medically Reviewed By:
Mark Arredondo, M.D.

MONDAY, April 17, 2023 (HealthDay News) -- α-synuclein seed amplification assays (SAAs) can classify people with Parkinson disease with high sensitivity and specificity, according to a study published in the May issue of The Lancet Neurology.

Andrew Siderowf, M.D., from the University of Pennsylvania in Philadelphia, and colleagues assessed the diagnostic performance of the α-synuclein SAA in a cross-sectional analysis based on assessments conducted at enrollment for Parkinson's Progression Markers Initiative (PPMI) cohort participants from 33 participating academic neurology outpatient practices worldwide. The sensitivity and specificity of the α-synuclein SAA was examined in participants with Parkinson disease and healthy controls.

The analysis included 1,123 participants: 545 with Parkinson disease, 163 healthy controls, 54 participants with scans without evidence of dopaminergic deficit, 51 prodromal participants, and 310 nonmanifesting carriers. The researchers found that for Parkinson disease, sensitivity was 87.7 percent and specificity was 96.3 percent for healthy controls. Overall, α-synuclein SAA had sensitivity of 98.6 percent in sporadic Parkinson disease with the typical olfactory deficit. In subgroups including LRRK2 Parkinson disease and participants with sporadic Parkinson disease without olfactory deficit, the proportion of positive α-synuclein SAA was lower (67.5 and 78.3 percent, respectively). An even lower α-synuclein SAA positivity rate was seen for participants with the LRRK2 variant and normal olfaction (34.7 percent). Eighty-six percent of participants with rapid eye movement sleep behavior disorder and hyposmia (prodromal individuals) had positive α-synuclein SAA. Of the nonmanifesting carriers, 8 percent were positive.

"These findings have immediate implications for clinical trial design, both to identify pathologically defined subgroups of people with Parkinson's disease and to establish biomarker-defined at-risk cohorts," the authors write.

Several authors disclosed financial ties to the pharmaceutical industry; PPMI is funded by multiple partners, including biopharmaceutical companies.

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