Increased Transferrin Sialylation Predicts Phenoconversion in Isolated REM Sleep Behavior Disorder

Sialic acid-protein interactions are involved in regulating central nervous system immunity; therefore, derangements in sialylation could be involved in neurodegeneration.

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.

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.

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).

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.