Apolipoprotein E deposition and astrogliosis are associated with maturation of beta-amyloid plaques in betaAPPswe 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 (Abeta) deposition. Previously, we have reported that the major species of Abeta in the amyloid plaques of Tg2576 mice are Abeta1-40 and Abeta1-42. Moreover, Abeta1-42 deposition precedes Abeta1-40 deposition, while Abeta1-40 accumulates in the central part of the plaques later in the pathogenic process. Those data indicate that Abeta 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 Abeta in amyloid plaques of aged Tg2576 mouse brains. Our findings suggest that Abeta1-42 deposition precedes apoE deposition, and that Abeta1-40 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 Alzheimer's disease with respect to apoE and astrogliosis. Furthermore, apoE deposition and astrogliosis may be necessary for amyloid plaque maturation.
Terai
K
K
Applied Pharmacology Research, Yamanouchi Pharmaceutical Co. Ltd., Tsukuba, Ibaraki, Japan. terai.kazuhiro@yamanouchi.co.jp
Iwai
A
A
Kawabata
S
S
Sasamata
M
M
Miyata
K
K
Yamaguchi
T
T
D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism; D019943:Amino Acid Substitution; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001253:Astrocytes / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D005911:Gliosis / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D009419:Nerve Tissue Proteins