Potential amyloid plaque-specific peptides for the diagnosis of Alzheimer's disease

Larbanoix, Lionel; Burtea, Carmen; Laurent, Sophie; Van Leuven, Fred; Toubeau, Gérard; Elst, Luce Vander; Muller, Robert N.

doi:10.1016/j.neurobiolaging.2008.09.021

« Previous Next »Neurobiology of Aging
Volume 31, Issue 10 , Pages 1679-1689, October 2010

Potential amyloid plaque-specific peptides for the diagnosis of Alzheimer's disease

Lionel Larbanoix
- Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, 24 Avenue du Champ de Mars, B-7000 Mons, Belgium
Carmen Burtea
- Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, 24 Avenue du Champ de Mars, B-7000 Mons, Belgium
Sophie Laurent
- Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, 24 Avenue du Champ de Mars, B-7000 Mons, Belgium
Fred Van Leuven
- Experimental Genetics Group, KULeuven, Herestraat 49, B-3000 Leuven, Belgium
Gérard Toubeau
- Department of Histology, University of Mons-Hainaut, 6 Avenue du Champ de Mars, B-7000 Mons, Belgium
Luce Vander Elst
- Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, 24 Avenue du Champ de Mars, B-7000 Mons, Belgium
Robert N. Muller
- Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, 24 Avenue du Champ de Mars, B-7000 Mons, Belgium
- Corresponding author. Tel.: +32 65 373520; fax: +32 65 373520.

Received 26 February 2008; received in revised form 23 June 2008; accepted 30 September 2008. published online 25 November 2008.

Abstract

Amyloid plaques (AP) represent one of the main molecular hallmarks of Alzheimer's disease (AD). In order to develop new AP-specific contrast agents for AD molecular imaging, the phage display technology was used to identify peptides specific to amyloid-beta (Aβ₄₂).

A random disulfide constrained heptapeptide phage display library was screened against Aβ₄₂. After biopanning, 72 phage clones were isolated and their binding affinity to Aβ₄₂ was evaluated by enzyme-linked immunosorbent assay (ELISA). The final library was enriched in two peptide sequences. The K_d of candidate phage clones for binding to Aβ₄₂ are in the picomolar range. The binding affinity for Aβ₄₂ of two selected peptides was confirmed by ELISA, and the specific interaction with AP was validated by immunohistochemistry on brain sections. The preliminary MRI in vivo study, which was performed with a peptide functionalized contrast agent on AD transgenic mouse, showed encouraging results.

To conclude, low molecular weight peptides presenting a specific affinity for Aβ₄₂ were identified by phage display. As specific carriers, they have a real potential for molecular imaging of AD thanks to AP binding.

Keywords: Alzheimer's disease, Amyloid-beta, Molecular imaging, Phage display, Amyloid plaques