Dynamic changes of oligomeric amyloid β levels in plasma induced by spiked synthetic Aβ42

Abstract

BackgroundA reliable blood-based assay is required to properly diagnose and monitor Alzheimer’s disease (AD). Many attempts have been made to develop such a diagnostic tool by measuring amyloid-β oligomers (AβOs) in the blood, but none have been successful in terms of method reliability. We present a multimer detection system (MDS), initially developed for the detection of prion oligomers in the blood, to detect AβOs.MethodsTo characterize Aβ in the blood, plasma was spiked with synthetic amyloid-β (Aβ) and incubated over time. Then, the MDS was used to monitor the dynamic changes of AβO levels in the plasma.ResultsIncreasing concentrations of AβOs were observed in the plasma of patients with AD but not in the plasma of normal control subjects. The plasma from patients with AD (n = 27) was differentiated from that of the age-matched normal control subjects (n = 144) with a sensitivity of 83.3% and a specificity of 90.0%.ConclusionsSynthetic Aβ spiked into the blood plasma of patients with AD, but that of not elderly normal control subjects, induced dynamic changes in the formation of AβOs over time. AβOs were detected by the MDS, which is a useful blood-based assay with high sensitivity and specificity for AD diagnosis.

Association of Plasma Oligomerized Beta Amyloid with Neurocognitive Battery Using Korean Version of Consortium to Establish a Registry for Alzheimer’s Disease in Health Screening Population

“…These blood-based biomarkers have demonstrated high correlation between the level of Aβ42, Aβ40, and the risk of AD [21,22], but they require highly sensitive equipment to detect low-concentrated target proteins. On the other hand, MDS-OAβ utilizes spiking of purified synthetic Aβ into plasma and incubation thereafter to measure the level of AβO tendencies in plasma [12]. The comparative measurement on the level of AβO tendencies in AD and normal plasma using MDS-OAβ was conducted and the resulting values were 1.43 ± 0.30 ng ml and 0.45 ± 0.19 ng/mL, respectively, showing the significant difference between the two groups (p < 0.001) [15].…”

“…Prior to the assay, aliquots of plasma samples were thawed at 37 • C for 15 min. All protocols were the same as in our previous papers [12,15,16]. As indicated in the assay protocol of the inBlood TM OAß Test, PBR-1 (purified synthetic Aβ made by PeopleBio Inc.) was spiked into plasma and the mixture was incubated at 37 • C for 48 h. The incubated plasma sample mixture and serially diluted standard samples were added to each well of the plates.…”

“…Various efforts are being made to detect oligomerized Aβ in biofluid [10,11] with the aim of validating it as the long-anticipated blood-based biomarker for AD diagnosis. Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) [12] is a technique which measures the level of the Aβ oligomerization (AβO) tendency after spiking purified synthetic Aβ into plasma samples. A previous study confirmed that the plasma OAβ level increases in plasma of AD patients but does not increase in the plasma of healthy normal control [12].…”

“…Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) [12] is a technique which measures the level of the Aβ oligomerization (AβO) tendency after spiking purified synthetic Aβ into plasma samples. A previous study confirmed that the plasma OAβ level increases in plasma of AD patients but does not increase in the plasma of healthy normal control [12]. The increase in the plasma AβO level in AD highly correlates with CSF Aβ42 and Pittsburgh compound B (PiB) PET standard uptake ratio [13].…”

The Propagation of Neurodegenerative Diseases by Inflammation and Exosomes

“…Since oAβ correlates with the synaptic loss and cognitive decline [21,22] and may be an early event in AD pathology, detection of oAβ in exosomes may be a useful early biomarker. Currently, oAβ has not been measured in plasma exosomes and oAβ in total plasma has not shown any differences between AD patients and controls [171,172]. However, a limitation of using plasma for this purpose is that the majority of the exosomes in plasma originate from erythrocytes and platelets, making the detection of the relatively few neuronal exosomes challenging.…”