A novel monoclonal antibody specific for the amino-truncated β-amyloid Aβ5-40/42 produced from caspase-cleaved amyloid precursor protein

Deposition of β-amyloid peptide (Aβ) as senile plaques and amyloid angiopathy are the major neuropathological features of Alzheimer's disease (AD). Heterogeneity is observed in the N- and C-termini of the deposited Aβ species. Recent evidence implicates caspase activation and apoptosis in AD neurodegeneration. We previously reported that a distinct N-terminally truncated Aβ species, Aβ5-40/42 is preferentially produced from the caspase-cleaved form of amyloid precursor protein (APP) lacking its C-terminal 31 amino acids and that it is deposited in AD brain tissues. Here, we generated a novel monoclonal antibody specific to the N-terminal end of Aβ5-40/42. Western blotting confirmed that this antibody recognizes Aβ5-40 but not Aβ1-40. We also showed that the antibody is able to immunoprecipitate Aβ5-40 but not Aβ1-40. Immunoprecipitation with the antibody followed by mass spectrometric analysis further detected Aβ5-40 in the conditioned media from neuroblastoma cells expressing the caspase-cleaved APP. The antibody reacted weakly with Aβ derived from AD brains. These results suggest that our novel monoclonal antibody is useful for detecting the N-terminally truncated Aβ produced in conjunction with caspase activation.