β-Amyloid peptides are key molecules that are involved in the pathology of Alzheimer's disease (AD). The source and place of the neurotoxic action of Aβ, however, is still a matter of controversial debates. In the present report, we studied the neuropathological events in a transgenic mouse model expressing human mutant β-amyloid precursor protein and human mutant presenilin-1 in neurons. Western blot and immunohistochemical analysis revealed that intracellular Aβ staining preceded plaque deposition, which started in the hippocampal formation. At later stages, many neuritic Aβ positive plaques were found in all cortical, hippocampal and many other brain areas. Interestingly, intraneuronal Aβ staining was no longer detected in the brain of aged double-transgenic mice, which correlates with the typical neuropathology in the brain of chronic AD patients.