beta-amyloid deposits in transgenic mice expressing human beta-amyloid precursor protein have the same characteristics as those in 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 amyloid-beta peptide (Abeta) deposition. We characterized Abeta deposits in the cerebral cortex biochemically and pathologically. A surface-enhanced laser desorption/ionization affinity mass spectrometric study using the 6E10 monoclonal antibody demonstrated that the major species of Abeta in a formic acid-extracted fraction of the cortex were Abeta(1-38), Abeta(1-40) and Abeta(1-42). Immunohistochemistry using antibodies to the carboxy-terminal epitopes of Abeta(1-40) and Abeta(1-42), as well as 6E10, showed that plaques containing Abeta(1-42) were more numerous than those containing Abeta(1-40) throughout the cortex. Laser confocal analysis of the immunoreactivities in the plaques demonstrated that Abeta(1-40) was preferentially located in the central part of the Abeta(1-42) positive plaques. Enzyme-linked immunosorbent assay measurements of Abeta(1-40) and Abeta(1-42) showed that Abeta(1-40) was several-fold more abundant than Abeta(1-42). From these data we suggest that Abeta(1-42) deposition may precede Abeta(1-40) deposition, while Abeta(1-40) begins to deposit in the central part of the plaques and accumulates there. Furthermore, localization of Abeta(1-40) corresponded almost exactly to congophilic structures, which were associated with aberrant swollen synapses detected with antibodies to synaptophysin and alpha-synuclein. Thus, Abeta deposits in Tg2576 mice have similar characteristics to those in Alzheimer's disease.
Terai
K
K
Applied Pharmacology Research, Yamanouchi Pharmaceutical Co. Ltd, 21, Miyukigaoka, Tsukuba, 305-8585, Ibaraki, Japan. terai.kazuhiro@yamanouchi.co.jp
Iwai
A
A
Kawabata
S
S
Tasaki
Y
Y
Watanabe
T
T
Miyata
K
K
Yamaguchi
T
T
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology; D016708:Synaptophysin / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C497604:SNCA protein, human; C497605:Snca protein, mouse; D016708:Synaptophysin; D051843:Synucleins; D051844:alpha-Synuclein; C078639:amyloid beta-protein (1-38); C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)