Current therapies for Alzheimer's disease only treat the symptoms of the 
disease. We have previously developed a novel monoclonal antibody, 2B3, which 
binds to the β-secretase cleavage site in amyloid precursor protein (APP) and 
reduces the production of amyloid-β (Aβ) in human cell lines. To determine 
whether the antibody was likely to be effective in mouse models of amyloid 
pathology in vivo, we investigated whether 2B3 could also bind to APP in mouse 
primary cortical neurones. Primary cortical neurones were produced from 
E15.5-17.5 C57Bl/6 wild-type and transgenic APP/V717I (London mutation) embryos. 
The percentage of the neuronal population was determined by immunocytochemistry. 
Cells were treated with 10 μg/ml 2B3 or an irrelevant IgG for 48 h and Aβ40 
levels determined by ELISA. The population of cells was found to contain over 
75% neurones and 2B3 bound effectively to these cells. No differences in Aβ40 
were detected between wild-type and transgenic cells. Importantly, 2B3 
significantly inhibited the production of Aβ40 by 75.15±1.37% of the media 
control, whereas an irrelevant IgG only significantly reduced Aβ40 levels by 
23.35±5.55% of the media control. The reduction in Aβ40 produced by 2B3 was 
significantly greater than that caused by the IgG. These data indicate that 2B3 
binds to APP in mouse neurones and can inhibit Aβ40, similar to our previous 
findings. The antibody is probably therefore acting by steric hindrance of 
β-secretase and these data suggest that it will be effective in mice in vivo and 
could be an alternative potential therapy for Alzheimer's disease.