Eun Seok Gil1, Anna Barnette2, Jinwoo Cheon3, Seong H. Kim2, and Tao L. Lowe4. (1) Department of Surgery, Pennsylvania State University, 500 University Drive, Hershey, PA 17033, (2) Chemical Engineering, Penn State University, 118-B Fenske Lab, University Park, PA 16802-4400, (3) Chemistry, Yonsei University, South Korea, (4) Departments of Surgery, Bioengineering, and Materials Science and Engineering, Pennsylvania State University, 500 University Drive, Hershey, PA 17033
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 Abƒnplaques 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 Abƒnoligomers. 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.