Microchip Electrophoresis Profiling of Aβ Peptides in the Cerebrospinal Fluid of Patients with Alzheimer's Disease

The preferential aggregation of A beta 1-42 in amyloid plaques is one of the major neuropathological events in Alzheimer's disease. This is accompanied by a relative reduction of the concentration of A beta 1-42 in the cerebrospinal fluid (CSF) of patients developing the signs of Alzheimer's disease. Here, we describe a microchip gel electrophoresis method in polydimethylsiloxane (PDMS) chip that enables rapid profiling of major All peptides in cerebrospinal fluid. To control the electroosmotic flow (EOF) in the PDMS channel and also to reduce the adsorption of the peptides to the surface of the channel, a new double coating using poly(dimethylacrylamide-co-ally1 glycidyl ether) (PDMA-AGE) and methylcellulose-Tween-20 was developed. With this method, separation of five synthetic Afi peptides (A beta 1-37, A beta 1-38, A beta 1-42, A beta 1-40, andA beta 1-42) was achieved, and relative abundance of A beta 1-42 to A beta 1-37 could be calculated in different standard mixtures. We applied our method for profiling of Afi peptides in CSF samples from nonAlzheimer patients and patients with Alzheimer's disease. A/I peptides in the CSF samples were captured and concentrated using a microfluidic system in which magnetic beads coated with anti-Afi were self-organized into an affinity microcolumn under the a permanent magnetic field. Finally, we could detect two iVI peptides (A beta 1-42 and A beta 1-42) in the CSF samples.