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 alpha-synuclein (alpha-syn), beta-amyloid(1-42) (A beta(1-42)) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of alpha-syn with A beta 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 alpha-syn (total and oligomeric), A beta(1-42) and tau (total and phosphorylated) in RBCs. Moreover, the presence of alpha-syn association with tau and A beta(1-42) 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 alpha-syn heterocomplexes with A beta(1-42) and tau in peripheral tissues; interestingly, alpha-syn-A beta(1-42) concentrations were increased in PD subjects with respect to healthy controls (HC), and directly correlated with disease severity and motor deficits. Moreover, total-alpha-syn levels were decreased in PD subjects and inversely related to their motor deficits. Finally, an increase of oligomeric-alpha-syn and phosphorylated-tau was observed in RBCs of the enrolled patients. The combination of three parameters (total-alpha-syn, phosphorylated-tau and alpha-syn-A beta(1-42) concentrations) provided the best fitting predictive index for discriminating PD patients from controls. Nevertheless further investigations should be required, overall, these data suggest alpha-syn hetero-aggregates in RBCs as a putative tool for the diagnosis of PD.