Antibody-bound β-amyloid precursor protein stimulates the production of tumor necrosis factor-α and monocyte chemoattractant protein-1 by cortical neurons

• Main Authors: Corinne Mbebi, Jose-Luis González de Aguilar, Violaine Sée, Luc Dupuis, Nelly Frossard, Luc Mercken, Laurent Pradier, Yves Larmet, Jean-Philippe Loeffler
• Format: Article
• Language: English
• Published: Elsevier 2005-06-01
• Series: Neurobiology of Disease
• Subjects: Alzheimer's disease; β-amyloid precursor protein; c-Jun N-terminal protein kinase; Monocyte chemoattractant protein-1; Neuronal death; Tumor necrosis factor-α
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996104002864

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the accumulation of extracellular depositions of fibrillar β-amyloid (Aβ), which is derived from the alternative processing of β-amyloid precursor protein (APP). Although APP is thought to function as a cell surface receptor, its mode of action still remains elusive. In this study, we found that the culture medium derived from cortical neurons treated with an anti-APP antibody triggers the death of naive neurons. Biochemical and immunocytochemical analyses revealed the presence, both in the conditioned medium and in neurons, of increased levels of tumor necrosis factor-α and monocyte chemoattractant protein-1. Furthermore, the expression of these proinflammatory mediators occurred through a c-Jun N-terminal protein kinase/c-Jun-dependent mechanism. Taken together, our findings provide evidence for a novel mechanism whereby neuronal APP in its full-length configuration induces neuronal death. Such a mechanism might be relevant to neuroinflammatory processes as those observed in AD.