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Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson’s disease

INTRODUCTION: Early 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 invo...

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Autores principales: Chen, Zhi-ting, Pan, Chu-zhui, Ruan, Xing-lin, Lei, Li-ping, Lin, Sheng-mei, Wang, Yin-zhou, Zhao, Zhen-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10546046/
https://www.ncbi.nlm.nih.gov/pubmed/37794977
http://dx.doi.org/10.3389/fnagi.2023.1216905
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author Chen, Zhi-ting
Pan, Chu-zhui
Ruan, Xing-lin
Lei, Li-ping
Lin, Sheng-mei
Wang, Yin-zhou
Zhao, Zhen-Hua
author_facet Chen, Zhi-ting
Pan, Chu-zhui
Ruan, Xing-lin
Lei, Li-ping
Lin, Sheng-mei
Wang, Yin-zhou
Zhao, Zhen-Hua
author_sort Chen, Zhi-ting
collection PubMed
description INTRODUCTION: Early 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. METHODS: Plasma 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. RESULTS: Neural-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. CONCLUSION: It 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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spelling pubmed-105460462023-10-04 Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson’s disease Chen, Zhi-ting Pan, Chu-zhui Ruan, Xing-lin Lei, Li-ping Lin, Sheng-mei Wang, Yin-zhou Zhao, Zhen-Hua Front Aging Neurosci Neuroscience INTRODUCTION: Early 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. METHODS: Plasma 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. RESULTS: Neural-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. CONCLUSION: It 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. Frontiers Media S.A. 2023-09-19 /pmc/articles/PMC10546046/ /pubmed/37794977 http://dx.doi.org/10.3389/fnagi.2023.1216905 Text en Copyright © 2023 Chen, Pan, Ruan, Lei, Lin, Wang and Zhao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Chen, Zhi-ting
Pan, Chu-zhui
Ruan, Xing-lin
Lei, Li-ping
Lin, Sheng-mei
Wang, Yin-zhou
Zhao, Zhen-Hua
Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson’s disease
title Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson’s disease
title_full Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson’s disease
title_fullStr Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson’s disease
title_full_unstemmed Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson’s disease
title_short Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson’s disease
title_sort evaluation of ferritin and tfr level in plasma neural-derived exosomes as potential markers of parkinson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10546046/
https://www.ncbi.nlm.nih.gov/pubmed/37794977
http://dx.doi.org/10.3389/fnagi.2023.1216905
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