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• W4229081306 abstract "For early diagnosis and disease monitoring of neurodegenerative diseases (NDs), reliable blood biomarkers are needed. Elevated levels of neurofilament light chain protein (NfL), an axonal damage marker, have been described across different NDs, with highest values in prion diseases and amyotrophic lateral sclerosis (ALS). Synaptic degeneration is a common early feature in most NDs and seems to precede neuronal degeneration in prion disease. However, synaptic markers in blood are still missing. Here, we investigated whether the brain-specific protein β-synuclein might be a suitable blood biomarker for early diagnosis and evaluation of synaptic integrity in prion disease.We analyzed blood β-synuclein with a newly established digital ELISA and NfL with a single-molecule array in samples obtained from human participants and prion and ALS animal models. Furthermore, β-synuclein was investigated in brain tissue of individuals with Creutzfeldt-Jakob disease (CJD) and controls.We investigated 308 patients, including 129 cases with prion disease, 8 presymptomatic PRNP variation carriers, 60 with ALS, 68 with other ND, and 43 control patients. In CJD symptomatic cases, β-synuclein and NfL were markedly increased compared to all other diagnostic groups (p < 0.001). In the large majority of presymptomatic PRNP variation carriers, β-synuclein and NfL levels were within normal ranges. In prion disease animal models, β-synuclein and NfL displayed normal levels in the presymptomatic phase with a sudden elevation at disease onset and a plateau in the symptomatic phase. In contrast to NfL, β-synuclein was not elevated in either symptomatic patients with ALS or an ALS animal model. In the discrimination between prion disease and all other groups, β-synuclein (area under the curve 0.97, 95% CI 0.94-0.99, p < 0.001) was superior to NfL (area under the curve 0.91, 95% CI 0.88-0.94, p < 0.001). In addition, brain tissue β-synuclein showed significantly reduced levels in patients with CJD compared to control patients (p < 0.001).Blood β-synuclein was significantly elevated in patients with CJD, reflecting ongoing synaptic damage, and showed good discriminative characteristics. We therefore propose it as a candidate blood marker for early diagnosis and monitoring of synaptic integrity in prion disease.This study provides Class III evidence that serum β-synuclein concentration accurately distinguishes patients with symptomatic CJD from controls." @default.
• W4229081306 created "2022-05-08" @default.
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• W4229081306 date "2022-04-05" @default.
• W4229081306 modified "2023-10-16" @default.
• W4229081306 title "Blood β-Synuclein and Neurofilament Light Chain During the Course of Prion Disease" @default.
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• W4229081306 doi "https://doi.org/10.1212/wnl.0000000000200002" @default.
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• W4229081306 hasPublicationYear "2022" @default.
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