(363c) Molecular Biosensors For Detection Of Beta-Amyloid Plaques And Oligomers

Beta-amyloid (Ab) is the major protein component of amyloid plaque deposits in Alzheimer's disease (AD) patients. It is considered that Ab oligomers are a biomarker for the AD diagnosis since they are related with the formation of toxic amyloid plaque formation. In this work, we develop novel molecular-level sensors containing poly(ethylene glycol) (PEG)-KLVFF (16-20 residue of Ab) as a recognition element for Ab plaques and oligomers. First, we use light scattering technique to study the interactions of the PEGylated KLVFF element with Ab. Second, we conjugate the PEGylated KLVFF element with a magnetic nanoparticle which serves as a magnetic resonance imaging (MRI) detecting element. The permeability of the developed PEGylated KLVFF-magnetic nanoparticle across bovine brain microvessel endothelial cell (BBMVEC) monolayer, an in vitro model of blood brain barrier, is investigated. The MRI detection sensitivity of the PEGylated KLVFF-magnetic nanoparticle to Ab?nplaques of human tissues is evaluated. Third, we nano-pattern the PEGylated KLVFF on a gold substrate, and use quartz crystal microbalance (QCM) technique to assess the detection sensitivity of the nano-patterned PEGylated KLVFF for toxic Ab?noligomers. In summary, this project provides novel insight to fabricate minimally invasive sensors for delection of Ab plaques and oligomers in AD via MRI and laboratory test of blood and cerebral spinal fluid samples.