Age-related amyloid beta protein accumulation induces cellular death and macrophage activation in transgenic mice

In view of the importance of amyloid beta protein accumulation in Alzheimer 's disease, this paper examines age-related amyloid beta protein (A beta) d eposition and accompanying cellular changes in a mouse model in vivo. Trans genic mice were studied which expressed a gene encoding 18 residues of sign al peptide and 99 residues of the carboxyl-terminal fragment (CTF) of the A beta precursor, under the control of the cytomegalovirus enhancer/chicken beta-actin promoter. In the pancreas, A beta accumulated in an age-dependen t manner. A beta deposits appeared as early as 3 weeks of age and increased in size and number from 4 to 16 months of age. The largest A beta deposits were observed in the transgenic pancreas at 16 and 20 months of age, Haema toxylin and eosin staining, macrophage immunostaining, and electron microsc opy showed that the A beta fibril deposits closely correlated with degenera tion of pancreatic acinar cells and macrophage activation. A beta 1-42 and A beta p3E-42 were predominant components of A beta deposits among amino- a nd carboxyl-terminal modified A beta species. These findings suggest that o verproduction of A beta causes age-related accumulation of A beta fibrils, with accompanying cellular degeneration and macrophage activation in vivo. Copyright (C) 2000 John Wiley & Sons, Ltd.