title: Generation and Partial Characterization of Rabbit Monoclonal Antibody to Amyloid-β Peptide 1-37 (Aβ37).
abstract: Secreted soluble amyloid-β 1-37 (Aβ37) peptide is one of the prominent Aβ forms next to Aβ40, and is found in cerebrospinal fluid (CSF) and blood. Recent studies have shown the importance of quantitation of CSF Aβ37 levels in combination with Aβ38, Aβ40, and Aβ42 to support the diagnosis of patients with probable Alzheimer's disease (AD), and the value of antibody to Aβ37 to facilitate drug discovery studies. However, the availability of reliable and specific monoclonal antibody to Aβ37 is very limited. Our aims were: 1) to generate and partially characterize rabbit monoclonal antibody (RabmAb) to Aβ37, and 2) to determine whether the antibody detects changes in Aβ37 levels produced by a γ-secretase modulator (GSM). Our generated RabmAb to Aβ37 was found to be specific to Aβ37, since it did not react with Aβ36, Aβ38, Aβ39, Aβ40, and Aβ42 in an ELISA or immunoblotting. The epitope of the antibody was contained in the seven C-terminal residues of Aβ37. The antibody was sensitive enough to measure CSF and plasma Aβ37 levels in ELISA. Immunohistological studies showed the presence of Aβ37-positive deposits in the brain of AD, and Down syndrome persons diagnosed with AD. Our studies also showed that the antibody detected Aβ37 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.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
authors.forename: Pankaj D
authors.initials: PD
authors.lastname: Mehta
authors.affiliation: FORUM Pharmaceuticals, Waltham, MA, USA.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Blain
authors.affiliation: FORUM Pharmaceuticals, Waltham, MA, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Freeman
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Patrick
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Barshatzky
authors.affiliation: FORUM Pharmaceuticals, Waltham, MA, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Hrdlicka
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
authors.forename: Sangita P
authors.initials: SP
authors.lastname: Mehta
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
authors.forename: Janusz
authors.initials: J
authors.lastname: Frackowiak
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
authors.forename: Bozena
authors.initials: B
authors.lastname: Mazur-Kolecka
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Wegiel
authors.affiliation: FORUM Pharmaceuticals, Waltham, MA, USA.
authors.forename: Holger
authors.initials: H
authors.lastname: Patzke
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Miller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004314:Down Syndrome / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007114:Immunization; D015151:Immunoblotting; D007150:Immunohistochemistry; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D011817:Rabbits; D012680:Sensitivity and Specificity
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D010446:Peptide Fragments; C078639:amyloid beta-protein (1-38); D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer disease; Down syndrome; ELISA; amyloid-β peptide; immunoblotting; immunohistochemistry; rabbit monoclonal antibodies to Aβ37