Intraneuronal APP/Aβ trafficking and plaque formation in β-amyloid precursor protein and presenilin-1 transgenic mice

Neuropil deposition of beta-amyloid peptides Abeta40 and Abeta42 is believed to be the key event in the neurodegenerative processes of Alzheimer's disease (AD). Since Abeta 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 Abeta 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 Abeta antibodies and defined their binding profile to APP, Abeta40 and Abeta42. Immunohistochemical staining revealed that intraneuronal Abeta40 and Abeta42 staining preceded plaque deposition, which started at 3 months of age. Abeta 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/Abeta transport problem and may be a model region to study APP/Abeta trafficking as an early pathological event.