Intraneuronal Aβ accumulation precedes plaque formation in β-amyloid precursor protein and presenilin-1 double-transgenic mice

beta -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 A beta, 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 beta -amyloid precursor protein and human mutant presenilin-1 in neurons. Western blot and immunohistochemical analysis revealed that intracellular A beta staining preceded plaque deposition, which started in the hippocampal formation. At later stages, many neuritic A beta positive plaques were found in all cortical, hippocampal and many other brain areas. Interestingly, intraneuronal A beta 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. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.