Imagine exosomes as tiny messengers traveling through the body, carrying important cargo. Scientists have investigated whether ferritin and TfR, two proteins involved in iron metabolism, can be detected in plasma neural-derived exosomes to identify potential markers for Parkinson’s disease (PD). By isolating these exosomes from PD patients and healthy controls, researchers found significantly higher levels of ferritin and TfR in the exosomes of PD patients. Remarkably, the levels of these proteins were positively correlated, suggesting a potential role in the excessive iron accumulation seen in PD. Further analysis using logistic regression models identified TfR as an independent predictor of the disease. Overall, the combination of ferritin and TfR showed promise as moderate diagnostic markers for PD. While the biomarkers did not correlate with disease progression, these findings open up new possibilities for early detection and understanding the mechanisms behind iron deposition in PD.

IntroductionEarly diagnosis of Parkinson’s disease (PD) remains challenging. It has been suggested that abnormal brain iron metabolism leads to excessive iron accumulation in PD, although the mechanism of iron deposition is not yet fully understood. Ferritin and transferrin receptor (TfR) are involved in iron metabolism, and the exosome pathway is one mechanism by which ferritin is transported and regulated. While the blood of healthy animals contains a plentiful supply of TfR-positive exosomes, no studies have examined ferritin and TfR in plasma neural-derived exosomes.MethodsPlasma exosomes were obtained from 43 patients with PD and 34 healthy controls. Neural-derived exosomes were isolated with anti-human L1CAM antibody immunoabsorption. Transmission electron microscopy and western blotting were used to identify the exosomes. ELISAs were used to quantify ferritin and TfR levels in plasma neural-derived exosomes of patients with PD and controls. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of ferritin and TfR. Independent predictors of the disease were identified using logistic regression models.ResultsNeural-derived exosomes exhibited the typical exosomal morphology and expressed the specific exosome marker CD63. Ferritin and TfR levels in plasma neural-derived exosomes were significantly higher in patients with PD than controls (406.46 ± 241.86 vs. 245.62 ± 165.47 ng/μg, P = 0.001 and 1728.94 ± 766.71 vs. 1153.92 ± 539.30 ng/μg, P < 0.001, respectively). There were significant positive correlations between ferritin and TfR levels in plasma neural-derived exosomes in control group, PD group and all the individuals (rs = 0.744, 0.700, and 0.752, respectively). The level of TfR was independently associated with the disease (adjusted odds ratio 1.002; 95% CI 1.000–1.003). ROC performances of ferritin, TfR, and their combination were moderate (0.730, 0.812, and 0.808, respectively). However, no relationship was found between the biomarkers and disease progression.ConclusionIt is hypothesized that ferritin and TfR in plasma neural-derived exosomes may be potential biomarkers for PD, and that they may participate in the mechanism of excessive iron deposition in PD.

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