Label-free detection of ApoE4-mediated beta-amyloid aggregation on single nanoparticle uncovering Alzheimer's disease

Abstract

Beta amyloid (A beta) deposition is a pathological milestone of Alzheimer's disease (AD). This is facilitated by an isoform of Apolipoprotein E4 (ApoE4), which is a dominant risk factor for AD. However, current in vitro A beta aggregation assays were performed in extreme conditions not linked to physiological conditions, to understand the mechanism of A beta induced neurotoxicity. Here, we present a simple method for the ApoE4-mediated A beta aggregation at physiological conditions using single gold nanoparticle based on localized surface plasmon resonance (LSPR). It can be directly observed by dark-field microscope or even by the naked eye. Following LSPR principles, we used ApoE4 inducing A beta 42 self-assemblies on gold nanoparticles (AuNPs) surface via their surface charge interaction. Using physiologically mimic cerebrospinal fluid, we determined a detection limit of 1.5 pM for A beta 42 corresponding to the similar to 2.9 nm LSPR-peak shift under ApoE4. Interestingly, the result also shows that ApoE4 induces the aggregation of A beta 42 more specifically and rapidly than that of A beta 40. This is the first biomimetic platform for real-time detection of A beta aggregation, mimicking biological conditions, which can be used to investigate AD directly. (C) 2015 Elsevier B.V. All rights reserved.