The deposition of amyloid β (Aβ) 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 β deposition and the type of Aβ 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 β deposits and the intrinsic rodent amyloid β deposits, that is, all plaques contained both human and mouse Aβ, and the diffuse amyloid β deposits also colocalized human and mouse Aβ. Furthermore, some blood vessels (mainly leptomeningeal vessels) show labeling with human Aβ, and most of these vessels also label with mouse Aβ. Our findings demonstrate that the human amyloid deposits in APP/PS1 transgenic mice are closely associated with mouse Aβ, however, they do not precisely overlap. For instance, the core of plaques consists of primarily human Aβ, whereas the rim of the plaque contains both human and mouse amyloid β, similarly, human and mouse Aβ are differentially localized in the blood vessel wall. Finally, as early as amyloid β deposits can be detected, they show the presence of both human and mouse Aβ. Together, these data indicate that mouse Aβ is formed and deposited in significant amounts in the AD mouse brain and that it is deposited together with the human Aβ. © 2006 Elsevier Inc. All rights reserved.