Detection of amyloid-b (Ab) aggregates contributes to the diagnosis of Alzheimer disease (AD). Plasma Ab is deemed a less invasive and more accessible hallmark of AD, as Ab can penetrate blood-brain barriers. However, correlations between biofluidic Ab concentrations and AD progression has been tenuous. Here, we introduce a diagnostic technique that compares the heterogeneous and the monomerized states of Ab in plasma. We used a small molecule, EPPS [4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid], to dissociate aggregated Ab into monomers to enhance quantification accuracy. Subsequently, Ab levels of EPPS-treated plasma were compared to those of untreated samples to minimize inter- and intraindividual variations. The interdigitated microelectrode sensor system was used to measure plasma Ab levels on a scale of 0.1 pg/ml. The implementation of this self-standard blood test resulted in substantial distinctions between patients with AD and individuals with normal cognition (NC), with selectivity and sensitivity over 90%.
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