Increased Transferrin Sialylation Predicts Phenoconversion in Isolated REM Sleep Behavior Disorder.

Content Provider	Europe PMC
Author	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
Abstract	AbstractBackgroundSialic acid–protein interactions are involved in regulating central nervous system immunity; therefore, derangements in sialylation could be involved in neurodegeneration.ObjectivesWe 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.MethodsSixty 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 (CDTadj). Dopamine transporter single‐photon emission computed tomography (DaT‐SPECT) imaging was performed. In iRBD, phenoconversion risk of DaT‐SPECT and CDTadj was evaluated using Cox regression adjusted for age and sex.ResultsMedian CDTadj 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 CDTadj 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 CDTadj levels (P = 0.189), low CDTadj 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).ConclusionsDecreased serum CDTadj is associated with substantia nigra degeneration in synucleinopathies. iRBD patients with low CDTadj 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.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC9305135&blobtype=pdf
Page Count	10
ISSN	08853185
Journal	Movement Disorders [Mov Disord]
Volume Number	37
DOI	10.1002/mds.28942
PubMed Central reference number	PMC9305135
Issue Number	5
PubMed reference number	35128728
e-ISSN	15318257
Language	English
Publisher	John Wiley & Sons, Inc.
Publisher Date	2022-02-07
Publisher Place	Hoboken, USA
Access Restriction	Open
Rights License	This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
Subject Keyword	Parkinson's disease rapid eye movement sleep behavior disorder transferrin sialylation phenoconversion
Content Type	Text
Resource Type	Article
Subject	Neurology Neurology (clinical)