Alpha-Synuclein Heteromers In Red Blood Cells Of Alzheimer'S Disease And Lewy Body Dementia Patients

Background: Red blood cells (RBCs) contain the majority of alpha-synuclein (alpha-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 alpha-syn, amyloid-beta (A beta(1-42)), 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 alpha-syn, A beta(1-42), tau, and their heteroaggregates (alpha-syn/A beta(1-42) and alpha-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 alpha-syn and tau concentrations as well as alpha-syn/tau heterodimers were significantly lower in the LBD group and the AD group compared with HC, whereas alpha-syn/A beta(1-42) concentrations were significantly lower in the AD dementia group only. RBC alpha-syn/tau heterodimers had a higher diagnostic accuracy for differentiating patients with LBD versus HC (AUROC= 0.80).Conclusion: RBC alpha-syn heteromers may be useful for differentiating between neurodegenerative dementias (LBD and AD) and HC. In particular, RBC alpha-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 alpha-syn, A beta(1-42), and tau interact in vivo to promote the aggregation and accumulation of each other.