N-truncated A¦Â peptides in complex fluids unraveled by new specific immunoassays

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• 作者：S&#233 ; bastien Ranaldi^a ; C&#233 ; line Caillava^b ; Sylvie Prom&#233 ; ^a ; Laetitia Rubrecht^a ; Sandra Cobo^a ; Nicolas Salvetat^a ; Emilie du Paty^a ; Pascale Galea^a ; Gudrun Aldrian^c ; Dung Le Nguyen^a ; Pierre Krolak-Salmon^d ; Franck Molina^a ; Daniel Laune^a ; Fr&#233 ; d&#233 ; ric Checler^b ; Jeannette Fareh^a ; Jean-Daniel Abraham^a ; ^{jean-daniel.abraham@sysdiag.cnrs.fr}
• 关键词：Alzheimer's disease ; Amyloid ; Truncated ; A¦ÂPP ; SELDI ; xMAP ; Diagnosis
• 刊名：Neurobiology of Aging
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：34
• 期：2
• 页码：523-539
• 全文大小：3272 K

文摘

Previous studies have highlighted the potential physiopathological and diagnostic role of N- and C-terminally truncated amyloid-¦Â (A¦Â) peptides in Alzheimer's disease. However, our knowledge about their production remains incomplete, in part due to the lack of very specific and sensitive tools for their detection. We thus developed specific monoclonal antibodies that target either A¦Â11-x or A¦Â17-x species, which result from the combined cleavages by ¦Â/¦Ã- or ¦Á/¦Ã-secretases, respectively. The presence of A¦Â peptides truncated at residue 11 and 17 peptides was qualitatively and quantitatively assessed, using surface enhanced laser desorption ionization-time of flight mass spectrometry and xMAP (Multi-Analyte Profiling) immunoassays, in the supernatant of HEK293 cells that overexpress wild type or mutant A¦Â protein precursor or in which ¦Á- and ¦Â-secretase activities had been modulated. Our results show a differential secretion of A¦Â11-40 and A¦Â17-40 species by these HEK293 cell lines. Finally, A¦Â11-40 concentration in human cerebrospinal fluid (measured with the new xMAP immunoassays) from a first pilot study was higher in cerebrospinal fluid samples from patients with Alzheimer's disease than in samples from patients with other types of dementia.