β-amyloid deposits in transgenic mice expressing human β-amyloid precursor protein have the same characteristics as those in Alzheimer's disease

A transgenic mouse expressing the human β-amyloid precursor protein with the “Swedish” mutation, Tg2576, was used to investigate the mechanism of amyloid-β peptide (Aβ) deposition. We characterized Aβ 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 Aβ in a formic acid-extracted fraction of the cortex were Aβ 1–38, Aβ 1–40 and Aβ 1–42. Immunohistochemistry using antibodies to the carboxy-terminal epitopes of Aβ 1–40 and Aβ 1–42, as well as 6E10, showed that plaques containing Aβ 1–42 were more numerous than those containing Aβ 1–40 throughout the cortex. Laser confocal analysis of the immunoreactivities in the plaques demonstrated that Aβ 1–40 was preferentially located in the central part of the Aβ 1–42 positive plaques. Enzyme-linked immunosorbent assay measurements of Aβ 1–40 and Aβ 1–42 showed that Aβ 1–40 was several-fold more abundant than Aβ 1–42. From these data we suggest that Aβ 1–42 deposition may precede Aβ 1–40 deposition, while Aβ 1–40 begins to deposit in the central part of the plaques and accumulates there. Furthermore, localization of Aβ 1–40 corresponded almost exactly to congophilic structures, which were associated with aberrant swollen synapses detected with antibodies to synaptophysin and α-synuclein. Thus, Aβ deposits in Tg2576 mice have similar characteristics to those in Alzheimer's disease.