Intraneuronal APP/A[beta] Trafficking and Plaque Formation in [beta]-Amyloid Precursor Protein and Presenilin-1 Transgenic Mice.
Wirths, Oliver 1; Multhaup, Gerd 4; Czech, Christian 2; Feldmann, Nicole 1; Blanchard, Veronique 2; Tremp, Gunter 3; Beyreuther, Konrad 4; Pradier, Laurent 2; Bayer, Thomas A. 1
[Review] Brain Pathology. 12(3):275-286, July 2002.

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Neuropil deposition of [beta]-amyloid peptides A[beta]40 and A[beta]42 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 V717I) 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[beta]40 and A[beta]42. Immunohistochemical staining revealed that intraneuronal A[beta]40 and A[beta]42 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.

(C) 2002, International Society of Neuropathology