Generation And Partial Characterization Of Rabbit Monoclonal Antibody To Amyloid-Beta Peptide 1-37 (A Beta(37))

Secreted soluble amyloid- beta 1- 37 (A beta(37)) peptide is one of the prominent A beta forms next to A beta(40), and is found in cerebrospinal fluid (CSF) and blood. Recent studies have shown the importance of quantitation of CSF A beta(37) levels in combination with A beta(38), A beta(40), and A beta(42) to support the diagnosis of patients with probable Alzheimer's disease (AD), and the value of antibody to A beta(37) to facilitate drug discovery studies. However, the availability of reliable and specific monoclonal antibody to A beta(37) is very limited. Our aims were: 1) to generate and partially characterize rabbit monoclonal antibody (RabmAb) to A beta(37), and 2) to determine whether the antibody detects changes in A beta(37) levels produced by a gamma-secretase modulator (GSM). Our generated RabmAb to A beta(37) was found to be specific to A beta(37), since it did not react with A beta(36), A beta(38), A beta(39), A beta(40), and A beta(42) in an ELISA or immunoblotting. The epitope of the antibody was contained in the seven C- terminal residues of A beta(37). The antibody was sensitive enough to measure CSF and plasma A beta(37) levels in ELISA. Immunohistological studies showed the presence of A beta(37)- positive deposits in the brain of AD, and Down syndrome persons diagnosed with AD. Our studies also showed that the antibody detected A beta(37) increases in CSF and brains of rodents following treatment with a GSM. Thus, our antibody can be widely applied to AD research, and in a panel based approach it may have potential to support the diagnosis of probable AD, and in testing the effect of GSMs to target AD.