Intraneuronal APP/Aβ Trafficking and Plaque Formation in β‐Amyloid Precursor Protein and Presenilin‐1 Transgenic Mice

Abstract

Neuropil deposition of β‐amyloid peptides Aβ40 and Aβ42 is believed to be the key event in the neurodegenerative processes of Alzheimer's disease (AD). Since Aβ seems to carry a transport signal that is required for axonal sorting of its precursor β‐amyloid precursor protein (APP), we studied the intraneuronal staining profile of Aβ peptides in a transgenic mouse model expressing human mutant APP751 (KM670/671NL and V717I) and human mutant presenilin‐1 (PS‐1 M146L) in neurons. Using surface plasmon resonance we analyzed the Aβ antibodies and defined their binding profile to APP, Aβ40 and Aβ42. Immunohistochemical staining revealed that intraneuronal Aβ40 and Aβ42 staining preceded plaque deposition, which started at 3 months of age. Aβ 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/Aβ transport problem and may be a model region to study APP/Aβ trafficking as an early pathological event.