Epitopes described in "Passive immunization against pyroglutamate-3 amyloid-β reduces plaque burden in Alzheimer-like transgenic mice: a pilot study."

Article Authors:Jeffrey L Frost; Bin Liu; Martin Kleinschmidt; Stephan Schilling; Hans-Ulrich Demuth; Cynthia A Lemere
Article Title:Passive immunization against pyroglutamate-3 amyloid-β reduces plaque burden in Alzheimer-like transgenic mice: a pilot study.
Reference Detail
Reference ID:1025041
Abstract:BACKGROUND: N-terminally truncated and modified pyroglutamate-3 amyloid- protein (pE3-A) is present in most, if not all, cerebral plaque and vascular amyloid deposits in human Alzheimer's disease (AD). pE3-A deposition is also found in AD-like transgenic (tg) mouse brain, albeit in lesser quantities than general A. pE3-A resists degradation, is neurotoxic, and may act as a seed for A aggregation. OBJECTIVE: We sought to determine if pE3-A removal by passive immunization with a highly specific monoclonal antibody (mAb) impacts pathogenesis in a mouse model of Alzheimer's amyloidosis. METHODS: APPswe/PS1E9 tg mice were given weekly intraperitoneal injections of a new anti-pE3-A mAb (mAb07/1) or PBS from 5.8 to 13.8 months of age (prevention) or from 23 to 24.7 months of age (therapeutic). Multiple forms of cerebral A were quantified pathologically and biochemically. Gliosis and microhemorrhage were examined. RESULTS: Chronic passive immunization with an anti-pE3-A mAb significantly reduced total plaque deposition and appeared to lower gliosis in the hippocampus and cerebellum in both the prevention and therapeutic studies. Insoluble A levels in hemibrain homogenates were not significantly different between immunized and control mice. Microhemorrhage was not observed with anti-pE3-A immunotherapy. CONCLUSIONS: Selective removal of pE3-A lowered general A plaque deposition suggesting a pro-aggregation or seeding role for pE3-A.
Affiliations:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass, USA.
Reference Type:Literature
PubMed ID:22343072
Journal:Neurodegener Dis
Journal Volume:10
Article Pages:265-70
Journal ISSN:1660-2854
Article Chemical List:Amyloid beta-Protein Precursor;Antibodies;Nerve Tissue Proteins;PSEN1 protein, human;Peptide Fragments;Presenilin-1;Pyrrolidonecarboxylic Acid
Article MeSH List:Alzheimer Disease(genetics; immunology; pathology; therapy); Amyloid beta-Protein Precursor(genetics); Amyloidosis(etiology; therapy); Animals; Antibodies(blood); Brain(pathology); Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Gliosis(etiology; therapy); Humans; Immunization, Passive(methods); Mice; Mice, Transgenic; Mutation(genetics); Nerve Tissue Proteins(metabolism); Peptide Fragments(immunology); Pilot Projects; Plaque, Amyloid(etiology; therapy); Presenilin-1(genetics); Pyrrolidonecarboxylic Acid(immunology); Statistics, Nonparametric; Time Factors
Curation Last Updated:2015-06-07 20:17:21