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Expression of human FE65 in amyloid precursor protein transgenic mice is associated with a reduction in β‐amyloid load
Author(s) -
SantiardBaron Dominique,
Langui Dominique,
Delehedde Maryse,
Delatour Benoît,
Schombert Brigitte,
Touchet Nathalie,
Tremp Günter,
Paul MarieFrançoise,
Blanchard Véronique,
Sergeant Nicolas,
Delacourte André,
Duyckaerts Charles,
Pradier Laurent,
Mercken Luc
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03026.x
Subject(s) - amyloid precursor protein , genetically modified mouse , signal transducing adaptor protein , transgene , p3 peptide , amyloid (mycology) , in vivo , microbiology and biotechnology , bace1 as , cortex (anatomy) , chemistry , biology , alzheimer's disease , medicine , biochemistry , neuroscience , signal transduction , gene , inorganic chemistry , disease
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 β‐amyloid (Aβ) 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 Aβ deposits at 6 months of age. Compared with APP mice, APP/FE65 double transgenic mice exhibited a lower Aβ accumulation in the cerebral cortex as demonstrated by immunohistochemistry and immunoassay, and a lower level of APP‐CTFs. The reduced accumulation of Aβ in APP/FE65 double transgenics, compared with APP mice, could be linked to the low Aβ42 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.