Cutaneous Phosphorylated Alpha-Synuclein in Lewy Body Dementia.
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Gibbons Christopher H, Levine Todd, Adler Charles H, Bellaire Bailey, Wang Ningshan, Agarwal Pinky, Aldridge Georgina M, Barboi Alexandru, Claassen Daniel, Evidente Virgilio G H, Galasko Douglas, Gonzalez-Duarte Alejandra, Gil Ramon, Gudesblatt Mark, Isaacson Stuart H, Kaufmann Horacio, Khemani Pravin, Kumar Rajeev, Lamotte Guillaume, Liu Andy J, McFarland Nikolaus R, Miglis Mitchell G, Reynolds Adam, Sahagian Gregory A, Saint-Hilaire Marie-Helene, Schwartzbard Julie B, Singer Wolfgang, Soileau Michael J, Vernino Steven, Millar Vernetti Patricio, Yerstein Oleg, Freeman Roy
Аннотация
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.