Soluble biomarkers of Alzheimer’s disease in plasma vary according to quantity of blood CNS derived extracellular vesicles

Abstract

AbstractBackgroundHallmark proteins pathogenic in Alzheimer’s disease (AD), amyloid and tau, can now be quantified in plasma samples using single‐molecule array (SIMOA). However, proteins are not only circulating in plasma, but are also present in nervous system‐derived extracellular vesicles (NDBEs) secreted by neurons in the plasma. We aim to quantify plasmatic NBDEs to evaluate whether their number or content are modified in symptomatic AD.MethodPlasma samples were obtained in clinically normal (CN) participants (N = 76, sex ratio F/M = 1.5, mean age 57.5 ± 16.3, Apoε4 positive n = 31, Apoε4 negative n = 43). Quantification of amyloid 42 – 40 peptides and total‐Tau protein was achieved with SIMOA multiplex analysis. For relative quantification of NDBEs circulating in plasma, we used DELFIA ELISA immunoassay with anti‐neuronal cell adhesion molecule (NCAM1) antibody. EVs content analysis was done with SIMOA Neurology 3‐plex A multiplex (t‐tau, Aβ42 and Aβ40).ResultWe observed that the relative amount of NDBEs in plasma was correlated with circulating Aβ42 (p < 0.0001, R² 0.2699) and t‐tau (p < 0.0001, R² 0.2753) such that greater numbers of NBDEs were associated with lower concentrations of proteins in circulating plasma. Content in Aβ42, Aβ40 and t‐Tau of NDBEs was higher in individuals with high amount of NDBEs circulating (Aβ42 (p < 0.05, R² = 0.18), Aβ40 (p < 0.05, R² = 0.18) and t‐tau (p < 0.03, R² = 0.17)).ConclusionThe number of NBDEs is negatively associated with the concentrations of these proteins, suggesting that these proteins are encapsulated in NBDEs. Latest results regarding NDBEs content seems to confirm this hypothesis with significant higher biomarkers concentrations in individuals with high amount of plasmatic NDBEs.