Development of Aβ terminal end-specific antibodies and sensitive ELISA for Aβ variant

Alzheimer's disease (AD) is a neurodegenerative affliction associated with memory dysfunction. Senile plaques are a pathological hallmark of AD, and amyloid beta (Abeta) peptides are a major component of these plaques. Abeta peptides are derived from proteolytic cleavage of the Abeta protein precursor (APP) by beta- and gamma-secretases to generate two principal species, Abeta1-40 and Abeta1-42. We have developed antibodies against the N- and C-termini of these peptides, and an ELISA for accurate and sensitive quantitative assessment. Sandwich ELISA composed of N-terminus (Abeta1) end-specific antibody, clone 82E1, and C-termini end-specific antibodies, and clones 1A10 and IC3 for Abeta40 and Abeta42, respectively, detects full-length Abeta1-40 and 1-42 with a sensitivity in the sub single digit fmol/ml (equivalent to single digit pg/ml) range with no cross-reactivity to APP. A combination of C-termini antibodies and an antibody against the middle region of Abeta detects mouse Abeta in non-transgenic mouse brains. (C) 2004 Elsevier Inc. All rights reserved.