Validation of CSF αSyn-SAA in an autopsy cohort with whole-body assessment of Lewy pathology
- 1Tokyo Metropolitan Institute for Geriatrics and Gerontology
Abstract
Background & Objectives: As recently recommended by neuropathologists, we assessed the diagnostic accuracy of cerebrospinal fluid (CSF) alpha-synuclein (-syn) seed amplification assay (SAA) in an autopsy cohort with systemic assessment of Lewy pathology. Methods: CSF was obtained antemortem and stored at -80 . -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 -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 -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 -syn SAA and Lewy pathology in the body.
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BibTeX
@misc{kurihara2026validation,
title = {{Validation of CSF αSyn-SAA in an autopsy cohort with whole-body assessment of Lewy pathology}},
author = {M. Kurihara and K. Satoh and T. Matsubara and M. I. Shimamura and A. Arakawa and M. Hara and K. Kanemaru and A. Iwata and S. Murayama and Y. Saito},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.02.26367119},
url = {https://www.medrxiv.org/content/10.64898/2026.11.02.26367119v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Validation of CSF αSyn-SAA in an autopsy cohort with whole-body assessment of Lewy pathology
AU - M. Kurihara
AU - K. Satoh
AU - T. Matsubara
AU - M. I. Shimamura
AU - A. Arakawa
AU - M. Hara
AU - K. Kanemaru
AU - A. Iwata
AU - S. Murayama
AU - Y. Saito
PY - 2026
DA - 2026/11/02
PB - medRxiv
DO - 10.64898/2026.11.02.26367119
UR - https://www.medrxiv.org/content/10.64898/2026.11.02.26367119v1
AB - Background & Objectives: As recently recommended by neuropathologists, we assessed the diagnostic accuracy of cerebrospinal fluid (CSF) alpha-synuclein (-syn) seed amplification assay (SAA) in an autopsy cohort with systemic assessment of Lewy pathology. Methods: CSF was obtained antemortem and stored at -80 . -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 -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 -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 -syn SAA and Lewy pathology in the body.
ER -