Objective: The study aimed to identify biomarkers of early-stage neurodegeneration in Parkinson’s disease (PD).

Background: The currently available diagnostic clinical criteria for PD enable diagnosis when the neurodegenerative process is already advanced. However, the optimal time window for potential PD disease-modifying therapy is at the early stage of neurodegeneration. Therefore, there is a strong need to identify biomarkers of early neurodegeneration of PD. As estrogen derivatives were previously shown to be involved in neuronal apoptosis and oxidative stress generation, the present study investigated their application as biomarkers of PD.

Method: The concentration of estrogens and their selected derivatives: hydroxy and methoxy estrogens, and H₂O₂ in blood serum was determined. The material was obtained from 16 patients with sporadic PD (8 women and 8 men, age of 63 years (±10), disease duration of 12 years (±3), H&Y score of 2.3 (±0.4). The control group was 9 healthy people (4 women and 5 men, age of 55(±10)). The LC-MS/MS was used to measure estrogens in the blood, whereas, by the stopped-flow method H₂O₂ was detected.

Results: The results showed an increased level of methoxyestrogens and H₂O₂ with a simultaneous decrease in the level of hydroxyestrogens in the blood of patients compared to the control group (p<10^-4). The measured concentration of 4-hydroxyestrone was five times lower in PD patients when compared with controls (p<10^-4), whereas 2-hydroxyestrone was not detected in PD patients. The 2-hydroxyestradiol values correlated with the age of patients and the severity of the disease. The level of 2-methoxyestradiol was twice higher, and 4-methoxyestron was 11 times higher in PD patients when compared to the control (p<10^-4). Interestingly, the level of H₂O₂ in healthy control was below the quantification threshold, i.e. below 10^-7 mol/dm³.

Conclusion: This is a first, still preliminary study showing significant differences in hydroxy and methoxyestrogens, and H₂O₂levels between PD patients and controls. Furthermore, we found that 2-hydroxyestradiol levels reflected the disease severity of PD. Based on the above, we suggest that plasma hydroxy and methoxy estrogens, as well as H₂O₂ may be applied as clinical biomarkers for PD diagnosis and treatment. Further research is required on a larger group of patients to replicate the findings.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/estrogen-derivatives-and-hydrogen-peroxide-as-promising-biomarkers-in-parkinsons-disease-preliminary-results/