Central and peripheral α-synuclein in Parkinson disease detected by seed amplification assay.

Autor: Chahine LM; Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Beach TG; Banner Sun Health Research Institute, Sun City, Arizona, USA., Adler CH; Department of Neurology, Mayo Clinic College of Medicine, Scottsdale, Arizona, USA., Hepker M; Biomedical Sciences, Iowa State University, Ames, Iowa, USA., Kanthasamy A; Center for Brain Science and Neurodegenerative Diseases, Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia, USA., Appel S; Biostatistics Analysis Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Pritzkow S; Department of Neurology, University of Texas, McGovern Medical School, Houston, Texas, USA., Pinho M; Department of Neurology, University of Texas, McGovern Medical School, Houston, Texas, USA., Mosovsky S; Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Serrano GE; Banner Sun Health Research Institute, Sun City, Arizona, USA., Coffey C; Banner Sun Health Research Institute, Sun City, Arizona, USA.; Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa, USA., Brumm MC; Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa, USA., Oliveira LMA; Banner Sun Health Research Institute, Sun City, Arizona, USA.; The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA., Eberling J; Banner Sun Health Research Institute, Sun City, Arizona, USA.; The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA., Mollenhauer B; Center of Parkinsonism and Movement Disorders, Department of Neurology, Paracelsus-Elena Klinik Kassel and University Medical Center Göttingen, Göttingen, Germany.
Jazyk: angličtina
Zdroj: Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2023 May; Vol. 10 (5), pp. 696-705. Date of Electronic Publication: 2023 Mar 27.
DOI: 10.1002/acn3.51753
Abstrakt: Objectives: Detection of α-synuclein aggregates by seed amplification is a promising Parkinson disease biomarker assay. Understanding intraindividual relationships of α-synuclein measures could inform optimal biomarker development. The objectives were to test accuracy of α-synuclein seed amplification assay in central (cerebrospinal fluid) and peripheral (submandibular gland) sources, compare to total α-synuclein measures, and investigate within-subject relationships.
Methods: The Systemic Synuclein Sampling Study aimed to characterize α-synuclein in multiple tissues and biofluids within Parkinson disease subjects (n = 59) and compared to healthy controls (n = 21). Motor and non-motor measures and dopamine transporter scans were obtained. Four measures of α-synuclein were compared: seed amplification assay in cerebrospinal fluid and formalin-fixed paraffin-embedded submandibular gland, total α-synuclein quantified in biofluids using enzyme-linked immunoassay, and aggregated α-synuclein in submandibular gland detected by immunohistochemistry. Accuracy of seed amplification assay for Parkinson disease diagnosis was examined and within-subject α-synuclein measures were compared.
Results: Sensitivity and specificity of α-synuclein seed amplification assay for Parkinson disease diagnosis was 92.6% and 90.5% in cerebrospinal fluid, and 73.2% and 78.6% in submandibular gland, respectively. 25/38 (65.8%) Parkinson disease participants were positive for both cerebrospinal fluid and submandibular gland seed amplification assay. Comparing accuracy for Parkinson disease diagnosis of different α-synuclein measures, cerebrospinal fluid seed amplification assay was the highest (Youden Index = 83.1%). 98.3% of all Parkinson disease cases had ≥1 measure of α-synuclein positive.
Interpretation: α-synuclein seed amplification assay (cerebrospinal fluid>submandibular gland) had higher sensitivity and specificity compared to total α-synuclein measures, and within-subject relationships of central and peripheral α-synuclein measures emerged.
(© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze: MEDLINE
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