α-Synuclein heteromers with ß-amyloid and tau decreased in red blood cells of Alzheimer’s disease and Lewy Body dementia patients.

Abstract

Background Red blood cells (RBC) account for more than 99% of α-syn concentrations in blood representing an interesting in vivo model for studying peripheral pathological alterations proved in neurodegeneration. The aim of the current study was to investigate the diagnostic value of total α-syn, Aβ 1-42 , tau and their heteroaggregates in RBCs of Lewy Body Dementias (LBDs) and Alzheimer’s disease (AD) patients compared to and healthy controls (HCs). Methods With a “home-made” sandwich enzyme-linked immunosorbent assay (ELISA) system, RBCs levels of total α-syn, Aβ 1-42 , tau and their heteroaggregates (α-syn/Aβ 1-42 and α-syn/tau) were measured in 27 subjects with LBDs (PDD, n = 17; DLB, n = 10), 51 subjects with AD (AD dementia, n = 37, prodromal AD, n = 14), and HC (n = 60). Results Compared with HC, total α-syn and tau concentrations as well as α-syn/tau heterodimers were significantly lower in LBDs group (p = 0.009, p = 0.009, and p < 0.001, respectively) and in AD group (p = 0.011, p = 0.003, and p < 0.001, respectively), whereas the heteroaggregates α-syn/Aβ 1-42 were significantly lower in AD dementia group (p < 0.001) only. RBC α-syn/tau heterodimers had the higher diagnostic accuracy for differentiating patients with LBD vs controls (AUROC = 0.80). Conclusion RBC α-syn heteroaggregates may be useful for differentiating between neurodegenerative dementias (LBD and AD) and healthy control. In particular, RBC α-syn/tau heterodimers have demonstrated good diagnostic accuracy for differentiating LBDs from HC. However, they are not consistently different between LBD and AD. Our findings also go beyond the clinical setting, suggesting that α-syn, Aβ 1-42 , and tau interact in vivo to promote the aggregation and accumulation of each other presumably accelerating cognitive dysfunction.