O. Wirths et al., Intraneuronal A beta accumulation precedes plaque formation in beta-amyloid precursor protein and presenilin-1 double-transgenic mice, NEUROSCI L, 306(1-2), 2001, pp. 116-120
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 pre
sent report, we studied the neuropathological events in a transgenic mouse
model expressing human mutant beta -amyloid precursor protein and human mut
ant presenilin-1 in neurons. Western blot and immunohistochemical analysis
revealed that intracellular A beta staining preceded plaque deposition, whi
ch started in the hippocampal formation. At later stages, many neuritic A b
eta positive plaques were found in all cortical, hippocampal and many other
brain areas. Interestingly, intraneuronal A beta staining was no longer de
tected in the brain of aged double-transgenic mice, which correlates with t
he typical neuropathology in the brain of chronic AD patients. (C) 2001 Els
evier Science Ireland Ltd. All rights reserved.