Microfluidic dissociation and clearance of Alzheimer’s β-amyloid aggregates
The abnormal aggregation of β-amyloid peptide (Aβ) 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 Aβ 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 Aβ aggregates using different types of metal chelators, (2) the clearance effect of deferoxamine on Aβ aggregates within microchannels, (3) comparison between destabilized Aβ dissociated from pre-formed Aβ aggregates and remaining deposits within the microchannels both before and after the clearance, and (4) secondary structure change in Aβ deposits by the clearance treatment. The microfluidics-based clearance system should be suitable for efficient screening of chemical candidates to enhance the clearance of Aβ deposits prior to their in vivo evaluation.
Journal: Biomaterials - Volume 31, Issue 26, September 2010, Pages 6789–6795