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 beta -amyloid precursor protein with the "Swedish" mutation, Tg2576, was used to investigate the mechanism of amyloid-beta peptide (A beta) deposition. We characterized A beta 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 A beta in a formic acid-extracted fraction of the cortex were A beta (1-38), A beta (1-10) and A beta (1-42) Immunohistochemistry using antibodies to the carboxy-terminal epitopes of A beta (1-40) and A beta (1-42), as well as 6E10, showed that plaques containing A beta (1-42) were more numerous than those containing A beta (1-40) throughout the cortex. Laser confocal analysis of the immunoreactivities in the plaques demonstrated that A beta (1-40) was preferentially located in the central part of the A beta (1-42) positive plaques. Enzyme-linked immunosorbent assay measurements of A beta (1-40) and A beta (1-42) showed that A beta (1-40) was several-fold more abundant than A beta (1-42). From these data we suggest that A beta (1-42) deposition may precede A beta (1-40) deposition, while A beta (1-40) begins to deposit in the central part of the plaques and accumulates there. Furthermore, localization of A beta (1-40) corresponded almost exactly to congophilic structures, which were associated with aberrant swollen synapses detected with antibodies to synaptophysin and alpha -synuclein. Thus, A beta deposits in Tg2576 mice have similar characteristics to those in Alzheimer's disease. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.