Deposition of mouse amyloid β in human APP/PS1 double and single AD model transgenic mice

The deposition of amyloid beta (A beta) peptides and neurofibrillary tangles are the two characteristic pathological features of Alzheimer's disease (AD). To investigate the relation between amyloid precursor protein (APP) production, amyloid beta deposition and the type of AD in deposits, i.e., human and/or mouse, we performed a histopathological analysis using mouse and human specific antibodies, of the neocortex and hippocampus in 6, 12 and 19 months old APP/PS1 double and APP and PS1 single transgenic mice. There was a significant correlation between the human amyloid beta deposits and the intrinsic rodent amyloid beta deposits, that is, all plaques contained both human and mouse A beta, and the diffuse amyloid P deposits also colocalized human and mouse A beta. Furthermore, some blood vessels (mainly leptomeningeal vessels) show labeling with human A beta, and most of these vessels also label with mouse A beta. Our findings demonstrate that the human amyloid deposits in APP/PS1 transgenic mice are closely associated with mouse A beta, however, they do not precisely overlap. For instance, the core of plaques consists of primarily human A beta, whereas the rim of the plaque contains both human and mouse amyloid beta, similarly, human and mouse A beta are differentially localized in the blood vessel wall. Finally, as early as amyloid 13 deposits can be detected, they show the presence of both human and mouse A beta. Together, these data indicate that mouse A beta is formed and deposited in significant amounts in the AD mouse brain and that it is deposited together with the human A beta. (c) 2006 Elsevier Inc. All rights reserved.