Since acid–protein interactions are crucial in regulating central nervous system inflammation, sialylation defects may be implicated in neurodegeneration. The variations in serum transferrin sialylation in prodromal and early-stage Parkinson’s disease (PD), their relationship to substantia nigra degradation, and the risk of phenoconversion to manifest illness were investigated by researchers for a study. About 60 treatment-naive patients with Parkinson’s disease (PD) were included, as were 72 polysomnography-confirmed isolated rapid eye movement sleep behavior disorder (iRBD) patients, i.e., patients with prodromal synucleinopathy, and 46 healthy volunteers aged ≥45 years and drinking ≤60 standard drinks per month. Using high-performance liquid chromatography, the fraction of serum low-sialylated, carbohydrate-deficient transferrin (CDT) isoforms was determined, and the results were corrected for alcohol consumption (CDTadj). In addition, imaging of the dopamine transporter single-photon emission computed tomography (DAT-SPECT) was done. The phenoconversion risk of DAT-SPECT and CDTadj in iRBD was assessed using Cox regression adjusted for age and gender.

PD had a lower median CDTadj (1.1 [interquartile range: 1.0–1.3]%) than controls (1.2 [1.1–1.6]%) (P=0.001). In iRBD, participants with aberrant DAT-SPECT had a lower median CDTadj (1.1 [0.9–1.3]%) than those with normal DaT-SPECT (1.3 [1.2–1.6]%) (P=0.005). After a median 44-month follow-up, 20% of iRBD patients had a manifest illness. Although CDTadj levels did not differ significantly between iRBD converters and non-converters (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). In synucleinopathies, decreased serum CDTadj was related to substantia nigra degeneration. Patients with iRBD who had low CDTadj were more likely to then convert to manifest illness.

Reference: movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28942