Alzheimer's disease (AD) affects over 5 million patients at costs exceeding 100 billion dollars annually. One of the primary causes attributed to AD is the oligomerization of the amyloid-� protein, known as amyloid derived diffusible ligands (ADDLs), which cause neurotoxicity. The pathway by which ADDLs enter the neuron remains unknown however, many researchers believe the receptors on the surface provide an important drug target. Therefore, we are developing a high-throughput drug assay capable of screening multiple drugs with neuron receptors by combining the tunability of localized surface plasmon resonance spectroscopy (LSPR) with the specificity of matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). In order to study and utilize these transmembrane proteins they are encased in Nanodiscs, a plasma membrane mimetic that stabilizes the receptors outside of the cell. LSPR monitors the binding of receptor filled Nanodiscs to the ADDLs, and MALDI confirms the success or failure of a drug in disrupting this binding. Herein we present our progress toward this assay by demonstrating the detection of empty and receptor filled Nanodiscs using these techniques.

Drug screening assay for Alzheimer's disease using localized surface plasmon resonance spectroscopy and MALDI mass spectrometry

243rd National Meeting (2012)

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