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Increased Transferrin Sialylation Predicts Phenoconversion in Isolated REM Sleep Behavior Disorder
Author(s) -
Ganapathy S. Ranjani,
Levová Kateřina,
Kotačková Lenka,
Trnka Jiří,
Zogala David,
Rusz Jan,
Zima Tomáš,
Devos David,
Šonka Karel,
Růžička Evžen,
Kalousová Marta,
Dušek Petr
Publication year - 2022
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.28942
Subject(s) - rem sleep behavior disorder , interquartile range , medicine , parkinson's disease , gastroenterology , hazard ratio , rapid eye movement sleep , substantia nigra , disease , psychology , endocrinology , confidence interval , electroencephalography , psychiatry
Background Sialic acid–protein interactions are involved in regulating central nervous system immunity; therefore, derangements in sialylation could be involved in neurodegeneration. Objectives We evaluate the differences in serum transferrin sialylation in prodromal and early‐stage Parkinson's disease (PD), its relation to substantia nigra degeneration, and the risk of phenoconversion to manifest disease. Methods Sixty treatment‐naive PD patients; 72 polysomnography‐confirmed isolated rapid eye movement sleep behavior disorder (iRBD) patients, that is, patients with prodromal synucleinopathy; and 46 healthy volunteers aged ≥45 years and drinking ≤60 standard drinks per month were included. The proportion of serum low‐sialylated, carbohydrate‐deficient transferrin (CDT) isoforms was assessed using high‐performance liquid chromatography, and the values were adjusted for alcohol intake (CDT adj ). Dopamine transporter single‐photon emission computed tomography (DaT‐SPECT) imaging was performed. In iRBD, phenoconversion risk of DaT‐SPECT and CDT adj was evaluated using Cox regression adjusted for age and sex. Results Median CDT adj was lower in PD (1.1 [interquartile range: 1.0–1.3]%) compared to controls (1.2 [1.1–1.6]%) ( P = 0.001). In iRBD, median CDT adj was lower in subjects with abnormal (1.1 [0.9–1.3]%) than normal (1.3 [1.2–1.6]%) DaT‐SPECT ( P = 0.005). After a median 44‐month follow‐up, 20% of iRBD patients progressed to a manifest disease. Although iRBD converters and nonconverters did not significantly differ in CDT adj levels ( P = 0.189), low CDT adj increased the risk of phenoconversion with hazard ratio 3.2 ( P = 0.045) but did not refine the phenoconversion risk associated with abnormal DaT‐SPECT yielding hazard ratio 15.8 ( P < 0.001). Conclusions Decreased serum CDT adj is associated with substantia nigra degeneration in synucleinopathies. iRBD patients with low CDT adj are more likely to phenoconvert to manifest disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.