Epitopes described in "A cyclic undecamer peptide mimics a turn in folded Alzheimer amyloid β and elicits antibodies against oligomeric and fibrillar amyloid and plaques."

Article Authors:Peter Hoogerhout; Willem Kamphuis; Humphrey F Brugghe; Jacqueline A Sluijs; Hans A M Timmermans; Janny Westdijk; Gijsbert Zomer; Claire J P Boog; Elly M Hol; Germie P J M van den Dobbelsteen
Article Title:A cyclic undecamer peptide mimics a turn in folded Alzheimer amyloid β and elicits antibodies against oligomeric and fibrillar amyloid and plaques.
Reference Detail
Reference ID:1021989
Abstract:The 39- to 42-residue amyloid (A) peptide is deposited in extracellular fibrillar plaques in the brain of patients suffering from Alzheimer's Disease (AD). Vaccination with these peptides seems to be a promising approach to reduce the plaque load but results in a dominant antibody response directed against the N-terminus. Antibodies against the N-terminus will capture A immediately after normal physiological processing of the amyloid precursor protein and therefore will also reduce the levels of non-misfolded A, which might have a physiologically relevant function. Therefore, we have targeted an immune response on a conformational neo-epitope in misfolded amyloid that is formed in advance of A-aggregation. A tetanus toxoid-conjugate of the 11-meric cyclic peptide A(22-28)-YNGK' elicited specific antibodies in Balb/c mice. These antibodies bound strongly to the homologous cyclic peptide-bovine serum albumin conjugate, but not to the homologous linear peptide-conjugate, as detected in vitro by enzyme-linked immunosorbent assay. The antibodies also bound--although more weakly--to A(1-42) oligomers as well as fibrils in this assay. Finally, the antibodies recognized A deposits in AD mouse and human brain tissue as established by immunohistological staining. We propose that the cyclic peptide conjugate might provide a lead towards a vaccine that could be administered before the onset of AD symptoms. Further investigation of this hypothesis requires immunization of transgenic AD model mice.
Affiliations:Department of Vaccinology, Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Peter.Hoogerhout@rivm.nl.
Reference Type:Literature
PubMed ID:21526148
Journal:PLoS One
Journal Volume:6
Article Pages:e19110
Journal ISSN:1932-6203
Article Chemical List:Amyloid beta-Peptides;Antibodies;Antigens;Peptides, Cyclic
Article MeSH List:Alzheimer Disease(immunology); Amino Acid Sequence; Amyloid beta-Peptides(chemistry; immunology); Animals; Antibodies(immunology); Antigens(immunology); Blotting, Western; Brain(pathology); Enzyme-Linked Immunosorbent Assay; Humans; Immunization; Immunohistochemistry; Mice; Molecular Sequence Data; Peptides, Cyclic(chemistry; immunology); Plaque, Amyloid(immunology); Protein Structure, Quaternary; Protein Structure, Secondary
Curation Last Updated:2015-06-07 20:04:14