Identification of peptides that specifically bind Aβ 1–40 amyloid in vitro and amyloid plaques in Alzheimer's disease brain using phage display

Abstract

The accumulation of the amyloid-β (Aβ) peptides in amyloid plaques correlates with pathologic changes that occur in the brains of patients with Alzheimer's disease (AD). The ability to directly target reagents to the amyloid form of the Aβ peptide may allow the delivery of neuroprotective agents to make amyloid plaques less toxic, the delivery of amyloid-destroying molecules to eliminate plaques, or the delivery of reagents to prevent amyloid plaque formation. In addition, such reagents may be useful as diagnostic tools to quantitate the extent of amyloid plaque formation in AD patients. As a step toward these goals, we have used phage peptide display technology to identify peptides that bind specifically to the amyloid form of the Aβ 1–40 peptide. Here we identify two 20-amino acid peptides with similar structural features that bind to the amyloid form of Aβ 1–40 but not to monomeric Aβ 1–40. A recombinant form of one of these peptides was produced in Escherichia coli as a fusion protein with thioredoxin. After purification, this reagent bound Aβ 1–40 amyloid in vitro with a K d of 60 nM and specifically labeled amyloid plaques in AD brains. A chemically synthesized version of this peptide also bound Aβ 1–40 amyloid and specifically stained amyloid plaques in AD brain. These peptide sequences represent new potential carrier molecules to deliver medicines to amyloid plaques in AD patients and to image plaques in AD brains.