title: Curcumin-conjugated nanoliposomes with high affinity for Aβ deposits: possible applications to Alzheimer disease.
abstract: Accumulation of amyloid peptide (Aβ) in senile plaques is a hallmark lesion of Alzheimer disease (AD). The design of molecules able to target the amyloid pathology in tissue is receiving increasing attention, both for diagnostic and for therapeutic purposes. Curcumin is a fluorescent molecule with high affinity for the Aβ peptide but its low solubility limits its clinical use. Curcumin-conjugated nanoliposomes, with curcumin exposed at the surface, were designed. They appeared to be monodisperse and stable. They were non-toxic in vitro, down-regulated the secretion of amyloid peptide and partially prevented Aβ-induced toxicity. They strongly labeled Aβ deposits in post-mortem brain tissue of AD patients and APPxPS1 mice. Injection in the hippocampus and in the neocortex of these mice showed that curcumin-conjugated nanoliposomes were able to specifically stain the Aβ deposits in vivo. Curcumin-conjugated nanoliposomes could find application in the diagnosis and targeted drug delivery in AD.
  
  
  BACKGROUND
  In this preclinical study, curcumin-conjugated nanoliposomes were investigated as possible diagnostics and targeted drug delivery system in Alzheimer's disease, demonstrating strong labeling of Aβ deposits both in human tissue and in mice, and in vitro downregulation of amyloid peptide secretion and prevention of Aβ-induced toxicity.
authors.affiliation: Laboratoire de Neuropathologie Escourolle, Hôpital de la Salpêtrière, AP-HP, 47 Bd de l'Hôpital, Paris, France.
authors.forename: Adina N
authors.initials: AN
authors.lastname: Lazar
authors.forename: Spyridon
authors.initials: S
authors.lastname: Mourtas
authors.forename: Ihsen
authors.initials: I
authors.lastname: Youssef
authors.forename: Christophe
authors.initials: C
authors.lastname: Parizot
authors.forename: Aurélien
authors.initials: A
authors.lastname: Dauphin
authors.forename: Benoît
authors.initials: B
authors.lastname: Delatour
authors.forename: Sophia G
authors.initials: SG
authors.lastname: Antimisiaris
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000302:isolation & purification; D000818:Animals; D001344:Autopsy; D004396:Coloring Agents / Q000008:administration & dosage / Q000737:chemistry; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D019579:Neocortex / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D008081:Liposomes; D010446:Peptide Fragments; D003474:Curcumin