Citations 2
Cutaneous Phosphorylated Alpha‐Synuclein in Lewy Body Dementia
Gibbons, Christopher H. , Levine, Todd, Bellaire, Bailey, Wang, Ningshan , Agarwal, Pinky , Aldridge, Georgina M. , Barboi, Alexandru, Claassen, Daniel O., Evidente, Virgilio G. H., Galasko, Douglas R., Gonzalez‐Duarte, Alejandra, Gil, Ramon, Gudesblatt, Mark , Khemani, Pravin , Kumar, Rajeev , Lamotte, Guillaume, Liu, Andy , Miglis, Mitchell G. , Reynolds, Adam , Sahagian, Gregory A., Saint‐Hilaire, Marie‐Helene, Schwartzbard, Julie, Yerstein, Oleg , Freeman, Roy, Claassen, Daniel O. , Liu, Andy , Claassen, Daniel , Miglis, Mitchell G , Singer, Wolfgang , Soileau, Michael J , Vernino, Steven , Freeman, Roy L. , Kaufmann, Horacio , Gibbons, Christopher , Adler, Charles H. , Evidente, Virgilio Gerald H. , Galasko, Douglas , González-Duarte, Alejandra , Isaacson, Stuart , Lamotte, Guillaume , McFarland, Nikolaus R. , Reynolds, Adam, Sahagian, Gregory , Vernino, Steven , Millar Vernetti, Patricio
Annals of Clinical and Translational Neurology | December 26, 2025 | Volume: 13 | Issue: 5 | Pages: 1041-1051
ABSTRACT Objective To determine the test performance of cutaneous phosphorylated alpha‐synuclein (P‐SYN) in dementia with Lewy bodies (DLB), individuals with reduced Montreal Cognitive Assessment (MoCA) and healthy controls. Methods This is the first subgroup analysis of the Synuclein‐One study, a prospective, blinded study evaluating P‐SYN detection from skin biopsies in 218 subjects with a referral diagnosis of control ( N = 151) and DLB ( N = 67). All subjects completed detailed examinations, questionnaires, and had skin biopsies for detection of P‐SYN. DLB patients were included if meeting the 4th DLB consensus probable criteria. Control subjects, aged 40–99, had no history, examination findings, or symptoms suggestive of a synucleinopathy or neurodegenerative disease. An expert review panel, blinded to pathological data, determined the final diagnosis. Controls with reduced MoCA (MoCA < 26, N = 26) at screening were analyzed separately. Results After expert panel review, only 50/67 patients met consensus criteria for DLB, 26/151 controls had a reduced MoCA, and 120/151 controls had a normal MoCA. The proportions of subjects with cutaneous P‐SYN detected by skin biopsy were 96.0% (48 of 50) of the DLB group, 31% (8 of 26) of the controls with reduced MoCA, and 3.3% (4 of 120) of the controls with normal MoCA. Interpretation In this prospective, blinded, cross‐sectional study, a high proportion of subjects meeting clinical consensus criteria for DLB had P‐SYN detected in skin biopsies. Almost 1/3 of subjects with reduced MoCA testing also had P‐SYN detected. These results support a role for skin biopsy detection of P‐SYN in patients with DLB. Trial Registration NCT04700722
Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients With Synucleinopathies
Levine, Todd, Bellaire, Bailey, Wang, Ningshan , Stohl, Jade, Aldridge, Georgina M. , Barboi, Alexandru , Evidente, Virgilio Gerald H. , Geschwind, Michael D. , Gil, Ramon, Gudesblatt, Mark , Khemani, Pravin , Liu, Andy , McFarland, Nikolaus R. , Miglis, Mitchell G. , Reynolds, Adam , Sahagian, Gregory , Saint-Hillaire, Marie-Helene, Schwartzbard, Julie, Yerstein, Oleg , Kaufmann, Horacio , Miglis, Mitchell G , McFarland, Nikolaus R , Gibbons, Christopher H. , Adler, Charles H. , Galasko, Douglas , González-Duarte, Alejandra , Isaacson, Stuart , Kumar, Rajeev , Lamotte, Guillaume , Reynolds, Adam, Singer, Wolfgang , Soileau, Michael J , Vernino, Steven , Freeman, Roy L. , Liu, Andy
JAMA | March 20, 2024 | Volume: 331 | Issue: 15 | Pages: 1298
ImportanceFinding 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.ObjectiveTo evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF.Design, Setting, and ParticipantsThis 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.ExposureSkin biopsy for detection of phosphorylated α-synuclein.Main OutcomesRates of detection of cutaneous α-synuclein in patients with PD, MSA, DLB, and PAF and controls without synucleinopathy.ResultsOf 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.Conclusions and RelevanceIn 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.