title: Beta-amyloid controls altered Reelin expression and processing in Alzheimer's disease.
abstract: Reelin is a glycoprotein that modulates synaptic function and plasticity in the mature brain, thereby favouring memory formation. We recently reported altered cerebral Reelin expression in Alzheimer's disease (AD). Here we demonstrate pronounced Reelin changes at protein and mRNA levels in the frontal cortex in adult Down's syndrome (DS), where the extra copy of chromosome 21 leads to overexpression of beta-amyloid. In cortical extracts of fetal DS samples we detected increased levels of the full-length Reelin and the 310-kDa fragment. Overexpression of mutant human amyloid precursor protein also led to an increase in levels of Reelin fragments in Tg2576 transgenic mice for human beta-amyloid. Finally, in vitro Abeta42 treatment of SH-SY5Y neuroblastoma cells led to increased Reelin levels. An altered pattern of Reelin glycosylation was detected in extracts from the frontal cortex of AD patients and in Abeta42-treated SH-SY5Y cells, supporting the notion that beta-amyloid triggers altered Reelin processing. These results provide evidence that Reelin expression and processing is altered in several amyloid conditions.
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, E-03550, Spain.
authors.forename: Arancha
authors.initials: A
authors.lastname: Botella-López
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Cuchillo-Ibáñez
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cotrufo
authors.forename: Su San
authors.initials: SS
authors.lastname: Mok
authors.forename: Qiao-Xin
authors.initials: QX
authors.lastname: Li
authors.forename: María-Sagrario
authors.initials: MS
authors.lastname: Barquero
authors.forename: Mara
authors.initials: M
authors.lastname: Dierssen
authors.forename: Eduardo
authors.initials: E
authors.lastname: Soriano
authors.forename: Javier
authors.initials: J
authors.lastname: Sáez-Valero
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005333:Fetus; D005786:Gene Expression Regulation / Q000502:physiology; D006031:Glycosylation; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases