Journal article
Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients With Synucleinopathies
JAMA : the journal of the American Medical Association, Vol.331(15), pp.1298-1306
04/16/2024
DOI: 10.1001/jama.2024.0792
PMCID: PMC10955354
PMID: 38506839
Abstract
Finding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]) is an urgent unmet need. Immunohistochemical detection of cutaneous phosphorylated α-synuclein may be a sensitive and specific clinical test for the diagnosis of synucleinopathies.
To evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF.
This blinded, 30-site, cross-sectional study of academic and community-based neurology practices conducted from February 2021 through March 2023 included patients aged 40 to 99 years with a clinical diagnosis of PD, DLB, MSA, or PAF based on clinical consensus criteria and confirmed by an expert review panel and control participants aged 40 to 99 years with no history of examination findings or symptoms suggestive of a synucleinopathy or neurodegenerative disease. All participants completed detailed neurologic examinations and disease-specific questionnaires and underwent skin biopsy for detection of phosphorylated α-synuclein. An expert review panel blinded to pathologic data determined the final participant diagnosis.
Skin biopsy for detection of phosphorylated α-synuclein.
Rates of detection of cutaneous α-synuclein in patients with PD, MSA, DLB, and PAF and controls without synucleinopathy.
Of 428 enrolled participants, 343 were included in the primary analysis (mean [SD] age, 69.5 [9.1] years; 175 [51.0%] male); 223 met the consensus criteria for a synucleinopathy and 120 met criteria as controls after expert panel review. The proportions of individuals with cutaneous phosphorylated α-synuclein detected by skin biopsy were 92.7% (89 of 96) with PD, 98.2% (54 of 55) with MSA, 96.0% (48 of 50) with DLB, and 100% (22 of 22) with PAF; 3.3% (4 of 120) of controls had cutaneous phosphorylated α-synuclein detected.
In this cross-sectional study, a high proportion of individuals meeting clinical consensus criteria for PD, DLB, MSA, and PAF had phosphorylated α-synuclein detected by skin biopsy. Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of phosphorylated α-synuclein in clinical care.
Details
- Title: Subtitle
- Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients With Synucleinopathies
- Creators
- Christopher H Gibbons - Beth Israel Deaconess Medical CenterTodd Levine - HonorHealthCharles Adler - Mayo Clinic in ArizonaBailey Bellaire - Synthetic GenomicsNingshan Wang - Beth Israel Deaconess Medical CenterJade Stohl - Synthetic GenomicsPinky Agarwal - Evergreen Health Medical CenterGeorgina M Aldridge - University of IowaAlexandru Barboi - NorthShore University HealthSystemVirgilio G H Evidente - Southwest Center for Chronic DiseaseDouglas Galasko - University of California, San DiegoMichael D Geschwind - University of California, San FranciscoAlejandra Gonzalez-Duarte - New York University School of MedicineRamon Gil - Parkinson's Disease Treatment Center of Southwest Florida, Port CharlotteMark Gudesblatt - New York UniversityStuart H Isaacson - Parkinson's Research and Education FoundationHoracio Kaufmann - New York UniversityPravin Khemani - Swedish Medical CenterRajeev Kumar - Rocky Mountain MS CenterGuillaume Lamotte - University of UtahAndy J Liu - Duke UniversityNikolaus R McFarland - University of Florida Health Science CenterMitchell Miglis - Stanford UniversityAdam Reynolds - Center for NeurosciencesGregory A Sahagian - Neurology Center of Southern CaliforniaMarie-Helene Saint-Hillaire - Boston Medical CenterJulie B Schwartzbard - Aventura Hospital and Medical CenterWolfgang Singer - Mayo ClinicMichael J Soileau - Texas Movement Disorder Specialists, GeorgetownSteven Vernino - The University of Texas Southwestern Medical CenterOleg Yerstein - Lahey Hospital and Medical CenterRoy Freeman - Beth Israel Deaconess Medical Center
- Resource Type
- Journal article
- Publication Details
- JAMA : the journal of the American Medical Association, Vol.331(15), pp.1298-1306
- Publisher
- American Medical Association (AMA)
- DOI
- 10.1001/jama.2024.0792
- PMID
- 38506839
- PMCID
- PMC10955354
- eISSN
- 1538-3598
- Language
- English
- Electronic publication date
- 03/20/2024
- Date published
- 04/16/2024
- Academic Unit
- Neurology; Iowa Neuroscience Institute
- Record Identifier
- 9984573658402771
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