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Cutaneous Phosphorylated Alpha-Synuclein in Lewy Body Dementia
Journal article   Open access   Peer reviewed

Cutaneous Phosphorylated Alpha-Synuclein in Lewy Body Dementia

Christopher H Gibbons, Todd Levine, Charles H Adler, Bailey Bellaire, Ningshan Wang, Pinky Agarwal, Georgina M Aldridge, Alexandru Barboi, Daniel Claassen, Virgilio G H Evidente, …
Annals of clinical and translational neurology, Vol.13(5), pp.1041-1051
05/2026
DOI: 10.1002/acn3.70291
PMCID: PMC13161868
PMID: 41449577
url
https://doi.org/10.1002/acn3.70291View
Published (Version of record) Open Access

Abstract

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. 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. 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. 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. NCT04700722.
 dementia with Lewy bodies synucleinopathy mild cognitive impairment skin biopsy

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