α-Synuclein Heteromers in Red Blood Cells of Alzheimer’s Disease and Lewy Body Dementia Patients
Simona Daniele, Filippo Baldacci, Rebecca Piccarducci, Giovanni Palermo, Linda Giampietri, Maria Laura Manca, Deborah Pietrobono, Daniela Frosini, Valentina Nicoletti, Gloria Tognoni, Filippo Sean Giorgi, Annalisa Lo Gerfo, Lucia Petrozzi, Chiara Cavallini, Ferdinando Franzoni, Roberto Ceravolo, Gabriele Siciliano, Maria Letizia Trincavelli, Claudia Martini, Ubaldo Bonuccelli
Abstract
BACKGROUND: Red blood cells (RBCs) contain the majority of α-synuclein (α-syn) in blood, representing an interesting model for studying the peripheral pathological alterations proved in neurodegeneration. OBJECTIVE: The current study aimed to investigate the diagnostic value of total α-syn, amyloid-β (Aβ1-42), tau, and their heteroaggregates in RBCs of Lewy body dementia (LBD) and Alzheimer's disease (AD) patients compared to healthy controls (HC). METHODS: By the use of enzyme-linked immunosorbent assays, RBCs concentrations of total α-syn, Aβ1-42, tau, and their heteroaggregates (α-syn/Aβ1-42 and α-syn/tau) were measured in 27 individuals with LBD (Parkinson's disease dementia, n = 17; dementia with Lewy bodies, n = 10), 51 individuals with AD (AD dementia, n = 37; prodromal AD, n = 14), and HC (n = 60). RESULTS: The total α-syn and tau concentrations as well as α-syn/tau heterodimers were significantly lower in the LBD group and the AD group compared with HC, whereas α-syn/Aβ1-42 concentrations were significantly lower in the AD dementia group only. RBC α-syn/tau heterodimers had a higher diagnostic accuracy for differentiating patients with LBD versus HC (AUROC = 0.80). CONCLUSION: RBC α-syn heteromers may be useful for differentiating between neurodegenerative dementias (LBD and AD) and HC. In particular, RBC α-syn/tau heterodimers have demonstrated good diagnostic accuracy for differentiating LBD from HC. However, they are not consistently different between LBD and AD. Our findings also suggest that α-syn, Aβ1-42, and tau interact in vivo to promote the aggregation and accumulation of each other.