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Generation and Partial Characterization of Rabbit Monoclonal Antibody to Amyloid-β Peptide 1-37 (Aβ37)
Pankaj D Mehta1, Jean-Francois Blain2, Emily A Freeman2
1New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
Journal of Alzheimer'S Disease : JAD
|February 23, 2017
Summary
A new antibody specifically detects amyloid-beta 37 (Aβ37) in cerebrospinal fluid and blood. This tool aids Alzheimer's disease diagnosis and drug discovery by measuring Aβ37 levels and their response to treatments.
Area of Science:
- Neuroscience
- Biochemistry
- Immunology
Background:
- Soluble amyloid-beta 37 (Aβ37) is a key form of amyloid-beta found in cerebrospinal fluid (CSF) and blood.
- Quantifying CSF Aβ37, alongside other Aβ forms, aids in diagnosing probable Alzheimer's disease (AD).
- Developing specific antibodies for Aβ37 is crucial for AD research and drug discovery, but reliable antibodies are scarce.
Purpose of the Study:
- To generate and characterize a novel rabbit monoclonal antibody (RabmAb) specific for Aβ37.
- To validate the antibody's specificity and sensitivity for detecting Aβ37 in biological samples.
- To assess the antibody's utility in monitoring Aβ37 changes induced by γ-secretase modulators (GSMs).
Main Methods:
- Generation and characterization of a rabbit monoclonal antibody (RabmAb) against Aβ37.
- Enzyme-linked immunosorbent assay (ELISA) and immunoblotting to confirm antibody specificity against various Aβ forms.
- ELISA for quantifying Aβ37 levels in human CSF and plasma.
- Immunohistological analysis of Aβ37 deposits in human brain tissue.
- Assessment of Aβ37 levels in rodent CSF and brain following GSM treatment.
Main Results:
- The generated RabmAb demonstrated high specificity for Aβ37, showing no cross-reactivity with other Aβ peptides (Aβ36, Aβ38-42).
- The antibody's epitope is localized within the C-terminal seven residues of Aβ37.
- The antibody successfully quantified Aβ37 in human CSF and plasma and detected Aβ37-positive deposits in AD and Down syndrome brains.
- Treatment with a GSM led to increased Aβ37 levels in rodent CSF and brains, as detected by the antibody.
Conclusions:
- A novel, highly specific monoclonal antibody for Aβ37 has been successfully developed.
- This antibody is a valuable tool for measuring Aβ37 in biological fluids and tissues, applicable to Alzheimer's disease research.
- The antibody can detect changes in Aβ37 levels, supporting its use in evaluating GSM efficacy for AD drug discovery and potentially aiding in diagnostic approaches.
