Intraneuronal APP/A beta trafficking and plaque formation in beta-amyloid precursor protein and presenilin-1 transgenic mice.

Neuropil deposition of beta-amyloid peptides A beta40 and A beta42 is believed to be the key event in the neurodegenerative processes of Alzheimer's disease (AD). Since A beta seems to carry a transport signal that is required for axonal sorting of its precursor beta-amyloid precursor protein (APP), we studied the intraneuronal staining profile of A beta peptides in a transgenic mouse model expressing human mutant APP751 (KM670/671NL and V7171) and human mutant presenilin-1 (PS-1 M146L) in neurons. Using surface plasmon resonance we analyzed the A beta antibodies and defined their binding profile to APP, A beta40 and A beta42. Immunohistochemical staining revealed that intraneuronal A beta40 and A beta42 staining preceded plaque deposition, which started at 3 months of age. A beta was observed in the somatodendritic and axonal compartments of many neurons. Interestingly, the striatum, which lacks transgenic APP expression harbored many plaques at 10 months of age. This is most likely due to an APP/A beta transport problem and may be a model region to study APP/A beta trafficking as an early pathological event.