Microfluidic dissociation and clearance of Alzheimer's beta-amyloid aggregates.

Abstract

The abnormal aggregation of beta-amyloid peptide (Abeta) in the brain is a major histopathological feature of Alzheimer's disease. Herein, we first report on microfluidic dissociation and clearance analysis of pre-formed Abeta aggregates for parallel screening of aggregate destabilizers. As a proof of the concept for the microfluidic platform, we investigated (1) microfluidics-based clearance of metal ion-induced Abeta aggregates using different types of metal chelators, (2) the clearance effect of deferoxamine on Abeta aggregates within microchannels, (3) comparison between destabilized Abeta dissociated from pre-formed Abeta aggregates and remaining deposits within the microchannels both before and after the clearance, and (4) secondary structure change in Abeta deposits by the clearance treatment. The microfluidics-based clearance system should be suitable for efficient screening of chemical candidates to enhance the clearance of Abeta deposits prior to their in vivo evaluation.