Journal article
Central and peripheral α-synuclein in Parkinson disease detected by seed amplification assay
Annals of Clinical and Translational Neurology, Vol.10(5), pp.696-705
05/01/2023
DOI: 10.1002/acn3.51753
PMCID: PMC10187727
PMID: 36972727
Abstract
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.
Details
- Title: Subtitle
- Central and peripheral α-synuclein in Parkinson disease detected by seed amplification assay
- Creators
- Lana M Chahine - University of PittsburghThomas G Beach - Banner Sun Health Research InstituteCharles H Adler - Mayo ClinicMonica Hepker - Iowa State UniversityAnumantha Kanthasamy - University of GeorgiaScott Appel - University of PennsylvaniaSandra Pritzkow - The University of Texas Health Science CenterMichelle Pinho - The University of Texas Health Science CenterSherri Mosovsky - University of PittsburghGeidy E Serrano - Banner Sun Health Research InstituteChristopher Coffey - University of IowaLuis M.A Oliveira - Banner Sun Health Research InstituteJamie Eberling - Banner Sun Health Research InstituteBrit Mollenhauer - Paracelsus Elena Klinik KasselKuldip DaveDanna JenningsJohn SeibylVanessa ArnedoLindsey RileyCarly LinderTatiana ForoudKatherine KopilDavid RussellPenelope HogarthRizwan AkhtarAmy AmaraConnie MarrasNaomi VisanjiDavid P BreenJohn CraryCharles WhiteDavid MunozChelsea Caspell-Garcia (Contributor)Systemic Synuclein Sampling Study
- Resource Type
- Journal article
- Publication Details
- Annals of Clinical and Translational Neurology, Vol.10(5), pp.696-705
- DOI
- 10.1002/acn3.51753
- PMID
- 36972727
- PMCID
- PMC10187727
- NLM abbreviation
- Ann Clin Transl Neurol
- ISSN
- 2328-9503
- Publisher
- John Wiley & Sons, Inc
- Language
- English
- Date published
- 05/01/2023
- Description audience
- Academic
- Academic Unit
- Biostatistics
- Record Identifier
- 9984459659302771
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