Validation of CSF αSyn-SAA in an autopsy cohort with whole-body assessment of Lewy pathology
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Background & Objectives: As recently recommended by neuropathologists, we assessed the diagnostic accuracy of cerebrospinal fluid (CSF) alpha-synuclein (α-syn) seed amplification assay (SAA) in an autopsy cohort with systemic assessment of Lewy pathology. Methods: CSF was obtained antemortem and stored at -80 ℃. α-syn SAA and systemic Lewy pathology assessment were conducted as previously reported. Kinetic parameters, including maximum fluorescence (Fmax) and time to reach 50% of Fmax (T50), were also evaluated. Results: CSF samples were available from 30 patients (8 with symptomatic Lewy body disease [LBD], 2 with multiple system atrophy [MSA], 3 with Alzheimer's disease [AD], and 17 disease controls). Despite different clinical stages, all patients with LBD had diffuse neocortical or limbic-stage pathology at autopsy, with widespread peripheral Lewy bodies, including in the esophagus, heart, and sympathetic ganglia. Lewy pathology was not observed in disease controls. SAA was positive in all 8 with LBD, low positive in one patient with AD, and negative in all others. Fmax was significantly higher in LBD compared with cases without α-syn pathology (9091±2083 vs. 1659±113 relative fluorescence units). The low-positive case had a lower positivity rate (25% vs. 75-100%), lower Fmax, and longer T50 than LBD cases. Conclusions: In this pilot study, CSF α-syn SAA demonstrated high specificity (95%) and high sensitivity (100%) for detecting LBD; however, all LBD cases had widespread pathology, including peripheral involvement. Larger studies are needed to understand the association between CSF α-syn SAA and Lewy pathology in the body.
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Validation of CSF αSyn-SAA in an autopsy cohort with whole-body assessment of Lewy pathology #NeuroDegeneration 🧪🧠 https://www.medrxiv.org/content/10.64898/2026.11.02.26367119v1
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