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

Article type: Research Article

Authors: Daniele, Simona^{a; 1} | Baldacci, Filippo^{b; 1} | Piccarducci, Rebecca^a | Palermo, Giovanni^b | Giampietri, Linda^b | Manca, Maria Laura^{b; c} | Pietrobono, Deborah^a | Frosini, Daniela^b | Nicoletti, Valentina^b | Tognoni, Gloria^b | Giorgi, Filippo Sean^b | Lo Gerfo, Annalisa^b | Petrozzi, Lucia^b | Cavallini, Chiara^a | Franzoni, Ferdinando^b | Ceravolo, Roberto^b | Siciliano, Gabriele^b | Trincavelli, Maria Letizia^a | Martini, Claudia^{a; *} | Bonuccelli, Ubaldo^{b; *}

Affiliations: [a] Department of Pharmacy, University of Pisa, Pisa, Italy | [b] Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy | [c] Department of Mathematics, University of Pisa, Pisa, Italy

Correspondence: [*] Correspondence to: Claudia Martini, Department of Pharmacy, Via Bonanno 6, 56126 Pisa, Italy. Tel.:+39 050 2219523; Fax:+39 050 2219608; E-mail: [email protected]. Ubaldo Bonuccelli, Department of Clinical and Experimental Medicine, Via Savi 10, 56126, Pisa, Italy. Tel.:+39 050 992443; Fax:+39 050 554808; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

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.

Keywords: α-Synuclein, Alzheimer’s disease, amyloid-β , Lewy body dementia, red blood cells

DOI: 10.3233/JAD-201038

Journal: Journal of Alzheimer's Disease, vol. 80, no. 2, pp. 885-893, 2021