CHANGES IN MORPHOLOGY OF NEUROBLASTOMA-CELLS TREATED WITH ALL-TRANS-RETINOIC ACID COMBINED WITH TRANSFER OF THE C-TERMINAL REGION OF THE AMYLOID PRECURSOR PROTEIN

Alzheimer disease is a progressive neurodegenerative disorder that is characterized by a loss of cognitive and memory functions. Amyloid fib rils deposited in neuritic plaque is mainly beta-amyloid protein (A be ta) that is derived from amyloid precursor protein (APP),The secreted form of APP, which is corresponded to N-terminal portion of APP, shows neurotrophic activities. On the other hand, A beta and cytoplasmic do mains of APP are thought to be neurotoxic. In order to investigate the effect of C-terminal fragment of APP covering A beta and the cytoplas mic domain upon cell growth and differentiation, we established a stab ly transfected cell line producing the C-terminal 100 amino acid pepti de of APP. The transfected clones stained positively with anti-A beta monoclonal antibody, TB-1. The growth rate of the transfected cells wa s not significantly different from that of mock-transfected cells or n ative NB39 cells. After treatment with ail-trans retinoic acid (ATRA), mock-transfected cells extended neurite processes and showed neuronal -like differentiation, while a transfected clone overexpressing C-term inal fragment did not present neuronal-like morphology. These results suggest that ATRA-induced neurite extension may be suppressed by overe xpression of the C-terminal fragment of APP. (C) 1998 Wiley-Liss, Inc.