Increased DJ-1 and α-Synuclein in Plasma Neural-Derived Exosomes as Potential Markers for Parkinson’s Disease

Abstract

The diagnosis of PD might be in difficulty, especially in the early stages. Therefore, the identification of novel biomarkers is imperative for the diagnosis and monitoring disease progression in PD. DJ-1 and α-synuclein, are two proteins that are critically involved in the pathogenesis of PD, and they have been examined as disease biomarkers in studies. However, no study exists regarding DJ-1 in plasma neural-derived exosomes. In the present study, the levels of DJ-1 and α-synuclein in plasma neural-derived exosomes were studied together in order to investigate novel biomarkers for PD. DJ-1 and α-synuclein in plasma and plasma neural-derived exosomes of the patients with PD and controls were quantified by ELISAs. The data revealed that the levels of DJ-1 and α-synuclein in plasma neural-derived exosomes and the ratio of plasma neural-derived exosomal DJ-1 to total DJ-1 were significantly higher in patients with PD, compared with controls, while levels of the two proteins in plasma exhibited no difference between the patients with PD and controls. However, no relationship was identified between biomarkers and disease progression. In addition, significant positive correlations between DJ-1 and α-synuclein in plasma neural-derived exosomes were found in the patients with PD and in healthy individuals. We hypothesize that DJ-1 in plasma neural-derived exosomes may be used as a potential biomarker as α-synuclein in PD and they might participate in the mechanism of PD together.

CNS-Derived Blood Exosomes as a Promising Source of Biomarkers: Opportunities and Challenges

“…Both, DJ-1 and α-synuclein were significantly higher in neuronal exosomes from patients with PD than in those from healthy controls whereas no significant differences were observed in total plasma, in agreement with the previous study by Shi et al (2014). As in the previous study, ROC analysis yielded only a moderate discrimination between patients with PD and healthy controls even when both biomarkers were combined (Zhao et al, 2019).…”

“…Recently, the protocol developed by Goetzl et al was used by another group to determine the levels of DJ-1 and α-synuclein in neuronal exosomes from 39 patients with PD and 40 healthy controls (Zhao et al, 2019). Both, DJ-1 and α-synuclein were significantly higher in neuronal exosomes from patients with PD than in those from healthy controls whereas no significant differences were observed in total plasma, in agreement with the previous study by Shi et al (2014).…”

“…They offer important advantages relative to expensive imaging modalities or the invasive lumbar puncture required for analysis of CSF biomarkers. However, drawbacks such as inconsistent results from different research groups and weak or non-existent correlation with disease severity or with CSF-derived or imaging biomarkers have hampered progress in this direction (Mehta and Adler, 2016;Lashley et al, 2018;Zhao et al, 2019). The relatively poor performance of blood-based biomarkers reflects the disconnect between the brain biochemistry and the blood composition, which is maintained by the BBB to protect the brain.…”

A longitudinal study on α‐synuclein in plasma neuronal exosomes as a biomarker for Parkinson’s disease development and progression

“…Comparisons of receiver operating characteristic results showed that neuronal exosomal α‐syn in our study had a greater power for diagnosing early‐stage PD. Other groups have reported mean values of 7.75 pg/mL by enzyme‐linked immunosorbent assay [12] or 25 pg/mL by Luminex [6] of α‐syn in plasma neuronal exosomes from patients with PD. We found a mean level of 2066 pg/mL of α‐syn using electrochemiluminescence immunoassay, which was reported to have a higher sensitivity and a larger dynamic range than traditional enzyme‐linked immunosorbent assay or Luminex [13].…”

A frontline defense against neurodegenerative diseases:the development of early disease detection methods

“…Indeed, erythrocytes can provide complementary information to plasma/serum biomarkers [25]. The implementation of blood-based biomarker panels with plasma neurally-derived exosomes and miRNA, besides the already established candidate molecules, may constitute the basis of a blood-based 'liquid biopsy' [26,27], following the encouraging developments of liquid biopsies in oncology.…”