title: Age-related amyloid beta protein accumulation induces cellular death and macrophage activation in transgenic mice.
abstract: In view of the importance of amyloid beta protein accumulation in Alzheimer's disease, this paper examines age-related amyloid beta protein (Abeta) deposition and accompanying cellular changes in a mouse model in vivo. Transgenic mice were studied which expressed a gene encoding 18 residues of signal peptide and 99 residues of the carboxyl-terminal fragment (CTF) of the Abeta precursor, under the control of the cytomegalovirus enhancer/chicken beta-actin promoter. In the pancreas, Abeta accumulated in an age-dependent manner. Abeta deposits appeared as early as 3 weeks of age and increased in size and number from 4 to 16 months of age. The largest Abeta deposits were observed in the transgenic pancreas at 16 and 20 months of age. Haematoxylin and eosin staining, macrophage immunostaining, and electron microscopy showed that the Abeta fibril deposits closely correlated with degeneration of pancreatic acinar cells and macrophage activation. Abeta1-42 and Abetap3E-42 were predominant components of Abeta deposits among amino- and carboxyl-terminal modified Abeta species. These findings suggest that overproduction of Abeta causes age-related accumulation of Abeta fibrils, with accompanying cellular degeneration and macrophage activation in vivo.
authors.affiliation: Department of Neurology, Gunma University School of Medicine, Maebashi, Gunma 371-8511, Japan. mshoji@akagi.sb
authors.forename: M
authors.initials: M
authors.lastname: Shoji
authors.forename: T
authors.initials: T
authors.lastname: Kawarabayashi
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: A
authors.initials: A
authors.lastname: Sasaki
authors.forename: T C
authors.initials: TC
authors.lastname: Saido
authors.forename: E
authors.initials: E
authors.lastname: Matsubara
authors.forename: Y
authors.initials: Y
authors.lastname: Tomidokoro
authors.forename: M
authors.initials: M
authors.lastname: Kanai
authors.forename: M
authors.initials: M
authors.lastname: Shizuka
authors.forename: K
authors.initials: K
authors.lastname: Ishiguro
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: Y
authors.initials: Y
authors.lastname: Harigaya
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
authors.forename: S
authors.initials: S
authors.lastname: Hirai
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D016923:Cell Death / Q000502:physiology; D008262:Macrophage Activation / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D016229:Amyloid beta-Peptides