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Front. Mol. Neurosci. | doi: 10.3389/fnmol.2018.00053

α-synuclein heterocomplexes with β-amyloid are increased in red blood cells of Parkinson’s Disease patients and correlate with disease severity

Simona Daniele1, Daniela Frosini2, Deborah Pietrobono1,  LUCIA PETROZZI2,  ANNALISA LO GERFO2, Filippo Baldacci2, Jonathan Fusi2,  Chiara Giacomelli1, Gabriele Siciliano2,  Maria Letizia Trincavelli1*, Ferdinando Franzoni2, Roberto Ceravolo2, Claudia Martini1 and Ubaldo Bonuccelli2
  • 1Department of Pharmacy, University of Pisa, Italy
  • 2Department of Clinical and Experimental Medicine, University of Pisa, Italy

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily -synuclein (-syn), -amyloid1-42 (A1-42) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of α-syn with A 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-Aβ concentrations were increased in PD subjects with respect to healthy controls, 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-Aβ 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.

Keywords: Parkinson’s disease, Neurodegenerative disorders, -synuclein, -amyloid, tau, -synuclein heterocomplexes

Received: 23 Nov 2017; Accepted: 07 Feb 2018.

Edited by:

Jean-Marc Taymans, Institut National de la Santé et de la Recherche Médicale (INSERM), France

Reviewed by:

Luigi Bubacco, Università degli Studi di Padova, Italy
Isabelle Landrieu, UMR8576 Unité de glycobiologie structurale et fonctionnelle, France  

Copyright: © 2018 Daniele, Frosini, Pietrobono, PETROZZI, LO GERFO, Baldacci, Fusi, Giacomelli, Siciliano, Trincavelli, Franzoni, Ceravolo, Martini and Bonuccelli. 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 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.

* Correspondence: Dr. Maria Letizia Trincavelli, University of Pisa, Department of Pharmacy, Pisa, Italy,