Apolipoprotein E deposition and astrogliosis are associated with maturation of beta-amyloid plaques in beta APPswe transgenic mouse: Implications forthe pathogenesis of Alzheimer's disease

A transgenic mouse expressing the human beta -amyloid precursor protein wit h 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) a nd 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 pla ques later in the pathogenic process. Those data indicate that A beta depos its in Tg2576 mice have similar characteristics to those in Alzheimer's dis ease. In the present study, to understand more fully the amyloid deposition mechanism implicating Alzheimer's disease pathogenesis, we examined immuno histochemically the distributions of apolipoprotein E (apoE) and A beta in amyloid plaques of aged Tg2576 mouse brains. Our findings suggest that A be ta (1-42) deposition precedes apoE deposition, and that A beta (1-40) depos ition follows apoE deposition during plaque maturation. We next examined th e relationship between apoE and astrogliosis associated with amyloid plaque s using a double-immunofluorescence method. Extracellular apoE deposits wer e always associated with reactive astrocytes whose processes showed enhance ment of apoE-immunoreactivity. Taken together, the characteristics of amylo id plaques in Tg2576 mice are similar to those in Alzheimers disease with r espect to apoE and astrogliosis. Furthermore, apoE deposition and astroglio sis may be necessary for amyloid plaque maturation. (C) 2001 Elsevier Scien ce B.V. All rights reserved.