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2009-04-01 - Colloque/Présentation - poster - Anglais - 1 page(s)

Larbanoix Lionel, Burtea Carmen , Laurent Sophie , Van Leuven Fred, Toubeau Gérard, Vander Elst Luce , Muller Robert , "Potential amyloid plaque-specific peptides for the diagnosis of Alzheimer’s disease" in Biomedica, Liège, Belgique, 2009

  • Codes CREF : Histologie (DI3212), Sciences biomédicales (DI3200), Biologie moléculaire (DI3111), Neuropathologie (DI332C), Chimie organique (DI1313), Chimie des colloïdes (DI1329), Imagerie médicale, radiologie, tomographie (DI3243)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108), Histologie (M118)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
  • Centres UMONS : Centre de Recherche en Microscopie et Imagerie Médicale (CMMI)

Abstract(s) :

(Anglais) The predominant cause of senile dementia is Alzheimer’s disease (AD), a progressive neurodegenerative disorder characterized by amyloid beta (A-beta) amyloidosis and tauopathy. A noninvasive method to detect the deposition of A-beta in amyloid plaques (AP) in the brain paremchyma will allow early diagnosis and preventive treatment before occurrence of neurological symptoms and irreversible neurodegeneration. In order to develop new AP-specific contrast agents for AD molecular imaging, the phage display technology was used to identify peptides that bind specifically to A-beta-42. A random disulfide constrained heptapeptide phage display library was screened against A-beta-42. After biopanning, 72 phage clones were isolated and their binding affinity to A-beta-42 was evaluated by ELISA. The genome sequencing of 22 selected phage clones showed the enrichment of the final library in two peptide sequences. The Kd of these 22 phage clones for binding to A-beta-42 are in the picomolar range. Two peptides expressed by the most efficient phage clones were synthesized and biotinylated. After confirming their binding affinity for A-beta-42 by ELISA, the specific interaction with AP was validated by immunohistochemistry on brain sections harvested from a transgenic mouse model of AD [2]. Preliminary MRI in vivo study, which was performed with peptide functionalized contrast agent in an AD transgenic mouse model, showed encouraging results. In conclusion, low molecular weight peptides presenting a specific affinity for A-beta-42 were identified by phage display. As specific carriers, they have a real potential for molecular imaging of AD thanks to AP binding. References [1] Larbanoix et al, Neurobiol aging, 2008, doi:10.1016/j.neurobiolaging.2008.09.021 [2] Van Dorpe et al, Am J Pathol., 157:1283-1298, 2000


Mots-clés :
  • (Anglais) Amyloid-beta
  • (Anglais) Phage display
  • (Anglais) peptides
  • (Anglais) Alzheimer’s disease
  • (Anglais) Amyloid plaques