Expression of human FE65 in amyloid precursor protein transgenic mice is associated with a reduction in beta-amyloid load.
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.
Santiard-Baron
Dominique
D
Neurodegenerative Diseases Group, Aventis, Vitry-sur-Seine, France.
Langui
Dominique
D
Delehedde
Maryse
M
Delatour
Benoît
B
Schombert
Brigitte
B
Touchet
Nathalie
N
Tremp
Günter
G
Paul
Marie-Françoise
MF
Blanchard
Véronique
V
Sergeant
Nicolas
N
Delacourte
André
A
Duyckaerts
Charles
C
Pradier
Laurent
L
Mercken
Luc
L
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
C091042:APBB1 protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins