title: Expression of human FE65 in amyloid precursor protein transgenic mice is associated with a reduction in beta-amyloid load.
abstract: FE65 is an adaptor protein that interacts with the cytoplasmic tail of the amyloid precursor protein (APP). In cultured non-neuronal cells, the formation of the FE65-APP complex is a key element for the modulation of APP processing, signalling and beta-amyloid (Abeta) production. The functions of FE65 in vivo, including its role in the metabolism of neuronal APP, remain to be investigated. In this study, transgenic mice expressing human FE65 were generated and crossbred with APP transgenic mice, known to develop Abeta deposits at 6 months of age. Compared with APP mice, APP/FE65 double transgenic mice exhibited a lower Abeta accumulation in the cerebral cortex as demonstrated by immunohistochemistry and immunoassay, and a lower level of APP-CTFs. The reduced accumulation of Abeta in APP/FE65 double transgenics, compared with APP mice, could be linked to the low Abeta42 level observed at 4 months of age and to the lower APP-CTFs levels. The present work provides evidence that FE65 plays a role in the regulation of APP processing in an in vivo model.
authors.affiliation: Neurodegenerative Diseases Group, Aventis, Vitry-sur-Seine, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Santiard-Baron
authors.forename: Dominique
authors.initials: D
authors.lastname: Langui
authors.forename: Maryse
authors.initials: M
authors.lastname: Delehedde
authors.forename: Benoît
authors.initials: B
authors.lastname: Delatour
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schombert
authors.forename: Nathalie
authors.initials: N
authors.lastname: Touchet
authors.forename: Günter
authors.initials: G
authors.lastname: Tremp
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Paul
authors.forename: Véronique
authors.initials: V
authors.lastname: Blanchard
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sergeant
authors.forename: André
authors.initials: A
authors.lastname: Delacourte
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: Laurent
authors.initials: L
authors.lastname: Pradier
authors.forename: Luc
authors.initials: L
authors.lastname: Mercken
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics
chemical_list: C091042:APBB1 protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins