α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson’s Disease Patients and Correlate with Disease Severity
Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1–42 (Aβ1–42) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of α-syn with Aβ or tau has gradua...
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doaj-b2216fc8bfcd4159826db0d3fe13f4da2020-11-24T23:01:59ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-02-011110.3389/fnmol.2018.00053333122α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson’s Disease Patients and Correlate with Disease SeveritySimona Daniele0Daniela Frosini1Deborah Pietrobono2Lucia Petrozzi3Annalisa Lo Gerfo4Filippo Baldacci5Jonathan Fusi6Chiara Giacomelli7Gabriele Siciliano8Maria Letizia Trincavelli9Ferdinando Franzoni10Roberto Ceravolo11Claudia Martini12Ubaldo Bonuccelli13Department of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyNeurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1–42 (Aβ1–42) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of α-syn with Aβ or tau has gradually emerged. Nevertheless, despite intensive research, NDs have no accepted peripheral markers for biochemical diagnosis. In this respect, Red Blood Cells (RBCs) are emerging as a valid peripheral model for the study of aging-related pathologies. Herein, a small cohort (N = 28) of patients affected by Parkinson’s disease (PD) and age-matched controls were enrolled to detect the content of α-syn (total and oligomeric), Aβ1–42 and tau (total and phosphorylated) in RBCs. Moreover, the presence of α-syn association with tau and Aβ1–42 was explored by co-immunoprecipitation/western blotting in the same cells, and quantitatively confirmed by immunoenzymatic assays. For the first time, PD patients were demonstrated to exhibit α-syn heterocomplexes with Aβ1–42 and tau in peripheral tissues; interestingly, α-syn-Aβ1–42 concentrations were increased in PD subjects with respect to healthy controls (HC), and directly correlated with disease severity and motor deficits. Moreover, total-α-syn levels were decreased in PD subjects and inversely related to their motor deficits. Finally, an increase of oligomeric-α-syn and phosphorylated-tau was observed in RBCs of the enrolled patients. The combination of three parameters (total-α-syn, phosphorylated-tau and α-syn-Aβ1–42 concentrations) provided the best fitting predictive index for discriminating PD patients from controls. Nevertheless further investigations should be required, overall, these data suggest α-syn hetero-aggregates in RBCs as a putative tool for the diagnosis of PD.http://journal.frontiersin.org/article/10.3389/fnmol.2018.00053/fullParkinson’s diseaseneurodegenerative disordersα-synucleinβ-amyloidtauα-synuclein heterocomplexes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Simona Daniele Daniela Frosini Deborah Pietrobono Lucia Petrozzi Annalisa Lo Gerfo Filippo Baldacci Jonathan Fusi Chiara Giacomelli Gabriele Siciliano Maria Letizia Trincavelli Ferdinando Franzoni Roberto Ceravolo Claudia Martini Ubaldo Bonuccelli |
spellingShingle |
Simona Daniele Daniela Frosini Deborah Pietrobono Lucia Petrozzi Annalisa Lo Gerfo Filippo Baldacci Jonathan Fusi Chiara Giacomelli Gabriele Siciliano Maria Letizia Trincavelli Ferdinando Franzoni Roberto Ceravolo Claudia Martini Ubaldo Bonuccelli α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson’s Disease Patients and Correlate with Disease Severity Frontiers in Molecular Neuroscience Parkinson’s disease neurodegenerative disorders α-synuclein β-amyloid tau α-synuclein heterocomplexes |
author_facet |
Simona Daniele Daniela Frosini Deborah Pietrobono Lucia Petrozzi Annalisa Lo Gerfo Filippo Baldacci Jonathan Fusi Chiara Giacomelli Gabriele Siciliano Maria Letizia Trincavelli Ferdinando Franzoni Roberto Ceravolo Claudia Martini Ubaldo Bonuccelli |
author_sort |
Simona Daniele |
title |
α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson’s Disease Patients and Correlate with Disease Severity |
title_short |
α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson’s Disease Patients and Correlate with Disease Severity |
title_full |
α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson’s Disease Patients and Correlate with Disease Severity |
title_fullStr |
α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson’s Disease Patients and Correlate with Disease Severity |
title_full_unstemmed |
α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson’s Disease Patients and Correlate with Disease Severity |
title_sort |
α-synuclein heterocomplexes with β-amyloid are increased in red blood cells of parkinson’s disease patients and correlate with disease severity |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2018-02-01 |
description |
Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1–42 (Aβ1–42) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of α-syn with Aβ or tau has gradually emerged. Nevertheless, despite intensive research, NDs have no accepted peripheral markers for biochemical diagnosis. In this respect, Red Blood Cells (RBCs) are emerging as a valid peripheral model for the study of aging-related pathologies. Herein, a small cohort (N = 28) of patients affected by Parkinson’s disease (PD) and age-matched controls were enrolled to detect the content of α-syn (total and oligomeric), Aβ1–42 and tau (total and phosphorylated) in RBCs. Moreover, the presence of α-syn association with tau and Aβ1–42 was explored by co-immunoprecipitation/western blotting in the same cells, and quantitatively confirmed by immunoenzymatic assays. For the first time, PD patients were demonstrated to exhibit α-syn heterocomplexes with Aβ1–42 and tau in peripheral tissues; interestingly, α-syn-Aβ1–42 concentrations were increased in PD subjects with respect to healthy controls (HC), and directly correlated with disease severity and motor deficits. Moreover, total-α-syn levels were decreased in PD subjects and inversely related to their motor deficits. Finally, an increase of oligomeric-α-syn and phosphorylated-tau was observed in RBCs of the enrolled patients. The combination of three parameters (total-α-syn, phosphorylated-tau and α-syn-Aβ1–42 concentrations) provided the best fitting predictive index for discriminating PD patients from controls. Nevertheless further investigations should be required, overall, these data suggest α-syn hetero-aggregates in RBCs as a putative tool for the diagnosis of PD. |
topic |
Parkinson’s disease neurodegenerative disorders α-synuclein β-amyloid tau α-synuclein heterocomplexes |
url |
http://journal.frontiersin.org/article/10.3389/fnmol.2018.00053/full |
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