Apolipoprotein E deposition and astrogliosis are associated with maturation of β-amyloid plaques in βAPPswe transgenic mouse:: Implications for the pathogenesis of Alzheimer's disease

A transgenic mouse expressing the human beta -amyloid precursor protein with the 'Swedish' mutation, Tg2576, was used to investigate the mechanism of beta -amyloid (AP) deposition. Previously, we have reported that the major species of A beta in the amyloid plaques of Tg2576 mice are A beta (1-40) and A beta (1-42). Moreover, A beta (1-42) deposition precedes A beta (1-40) deposition, while A beta (1-40) accumulates in the central part of the plaques later in the pathogenic process. Those data indicate that A beta deposits in Tg2576 mice have similar characteristics to those in Alzheimer's disease. In the present study, to understand more fully the amyloid deposition mechanism implicating Alzheimer's disease pathogenesis, we examined immunohistochemically the distributions of apolipoprotein E (apoE) and A beta in amyloid plaques of aged Tg2576 mouse brains. Our findings suggest that A beta (1-42) deposition precedes apoE deposition, and that A beta (1-40) deposition follows apoE deposition during plaque maturation. We next examined the relationship between apoE and astrogliosis associated with amyloid plaques using a double-immunofluorescence method. Extracellular apoE deposits were always associated with reactive astrocytes whose processes showed enhancement of apoE-immunoreactivity. Taken together, the characteristics of amyloid plaques in Tg2576 mice are similar to those in Alzheimers disease with respect to apoE and astrogliosis. Furthermore, apoE deposition and astrogliosis may be necessary for amyloid plaque maturation. (C) 2001 Elsevier Science B.V. All rights reserved.