Epitopes described in "Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis."

Article Authors:Jungsu Kim; Adam E M Eltorai; Hong Jiang; Fan Liao; Philip B Verghese; Jaekwang Kim; Floy R Stewart; Jacob M Basak; David M Holtzman
Article Title:Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis.
Reference Detail
Reference ID:1025481
Abstract:The apolipoprotein E (APOE) 4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). The influence of apoE on amyloid (A) accumulation may be the major mechanism by which apoE affects AD. ApoE interacts with A and facilitates A fibrillogenesis in vitro. In addition, apoE is one of the protein components in plaques. We hypothesized that certain anti-apoE antibodies, similar to certain anti-A antibodies, may have antiamyloidogenic effects by binding to apoE in the plaques and activating microglia-mediated amyloid clearance. To test this hypothesis, we developed several monoclonal anti-apoE antibodies. Among them, we administered HJ6.3 antibody intraperitoneally to 4-mo-old male APPswe/PS1E9 mice weekly for 14 wk. HJ6.3 dramatically decreased amyloid deposition by 60-80% and significantly reduced insoluble A40 and A42 levels. Short-term treatment with HJ6.3 resulted in strong changes in microglial responses around A plaques. Collectively, these results suggest that anti-apoE immunization may represent a novel AD therapeutic strategy and that other proteins involved in A binding and aggregation might also be a target for immunotherapy. Our data also have important broader implications for other amyloidosis. Immunotherapy to proteins tightly associated with misfolded proteins might open up a new treatment option for many protein misfolding diseases.
Affiliations:Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Reference Type:Literature
PubMed ID:23129750
Journal:J Exp Med
Journal Volume:209
Article Pages:2149-56
Journal ISSN:0022-1007
Article Chemical List:Amyloid beta-Peptides;Antibodies, Monoclonal;Apolipoproteins E
Article MeSH List:Amyloid beta-Peptides(metabolism); Amyloidosis(immunology; metabolism; prevention & control); Animals; Antibodies, Monoclonal(administration & dosage; blood; pharmacology); Apolipoproteins E(immunology; metabolism); Brain Diseases(immunology; metabolism; prevention & control); Enzyme-Linked Immunosorbent Assay; Immunoblotting; Immunoprecipitation; Immunotherapy(methods); Male; Mice; Mice, Transgenic; Statistics, Nonparametric
Curation Last Updated:2015-06-07 20:22:40