Transferrin Sialylation Predicts Phenoconversion in Isolated REM Sleep Behavior Disorder

Transferrin Sialylation Predicts Phenoconversion in Isolated REM Sleep Behavior Disorder

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 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 with substantia nigra degeneration. Patients with iRBD who had low CDTadj were more likely to phenoconvert to manifest illness.


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