EFFECT OF ALUMINUM ON EXPRESSION AND PROCESSING OF AMYLOID PRECURSOR PROTEIN

The environmental agent aluminium has been extensively investigated fo r a potential role in the aetiology of Alzheimer's disease, Despite ma ny investigations there is at present no definite proof for any involv ement, If aluminium is involved it is possible that its action is medi ated through interaction with the synthesis or processing of amyloid p recursor protein (APP). The present study compared aluminium loaded IM R-32 neuroblastoma cells and rat brains with control cells and brains to determine if aluminium affected APP expression and/or processing, I n the IMR-32 model system aluminium had no effect on steady-state APP mRNA levels or on the ratio of individual isoforms, It also had no qua ntitative or qualitative effect on APP-immunoreactive bands detected i n protein extracts from conditioned medium of these cells, In total ce ll extracts, aluminium reduced the intensity of APP-immunoreactive ban ds between 120-105 kDa but had no effect on a 9 kDa band, In rat brain s, aluminium had no effect on APP-immunoreactive bands from soluble or insoluble-membranous extracts, The results, in general, provide no ev idence for any effect of aluminium on APP expression or processing. (C ) 1996 Wiley-Liss, Inc.