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.

α-Synuclein Heteromers in Red Blood Cells of Alzheimer's Disease and Lewy Body Dementia Patients

Daniele, Simona
Co-primo
;
Baldacci, Filippo
Co-primo
;
Piccarducci, Rebecca;Palermo, Giovanni;Giampietri, Linda;Laura Manca, Maria;Pietrobono, Deborah;Frosini, Daniela;Nicoletti, Valentina;Tognoni, Gloria;Giorgi, Filippo Sean;Lo Gerfo, Annalisa;Petrozzi, Lucia;Cavallini, Chiara;Franzoni, Ferdinando;Ceravolo, Roberto;Siciliano, Gabriele;Trincavelli, Maria Letizia;Martini, Claudia
Penultimo
;
Bonuccelli, Ubaldo
Ultimo
2021-01-01

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.
2021
Daniele, Simona; Baldacci, Filippo; Piccarducci, Rebecca; Palermo, Giovanni; Giampietri, Linda; Laura Manca, Maria; Pietrobono, Deborah; Frosini, Daniela; Nicoletti, Valentina; Tognoni, Gloria; Giorgi, Filippo Sean; Lo Gerfo, Annalisa; Petrozzi, Lucia; Cavallini, Chiara; Franzoni, Ferdinando; Ceravolo, Roberto; Siciliano, Gabriele; Trincavelli, Maria Letizia; Martini, Claudia; Bonuccelli, Ubaldo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1082336
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