Epitopes described in "Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease."

Article Authors:M Britschgi; C E Olin; H T Johns; Y Takeda-Uchimura; M C LeMieux; K Rufibach; J Rajadas; H Zhang; B Tomooka; W H Robinson; C M Clark; A M Fagan; D R Galasko; D M Holtzman; M Jutel; J A Kaye; C A Lemere; J Leszek; G Li; E R Peskind; J F Quinn; J A Yesavage; J A Ghiso; T Wyss-Coray
Article Title:Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease.
Reference Detail
Reference ID:1016460
Abstract:A number of distinct beta-amyloid (Abeta) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural Abeta-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic Abeta and amyloidogenic non-Abeta species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21-89 years. Antibody reactivity was most prominent against oligomeric assemblies of Abeta and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of Abeta1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant Abeta, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from Abeta toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with Abeta the monkeys developed high titers not only against Abeta peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of Abeta antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD.
Affiliations:Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Reference Type:Literature
PubMed ID:19581601
Journal:Proc Natl Acad Sci U S A
Journal Volume:106
Article Pages:12145-50
Journal ISSN:0027-8424
Article Chemical List:Amyloid beta-Peptides;Antibodies;Immunoglobulin G;Neuroprotective Agents;Peptides
Article MeSH List:Aging(drug effects; immunology); Alzheimer Disease(blood; complications; immunology; pathology); Amyloid beta-Peptides(chemistry; immunology; toxicity); Animals; Antibodies(blood; cerebrospinal fluid; immunology); Cytoprotection(drug effects); Dementia(complications; immunology); Disease Progression; Genes, Dominant; Immunization; Immunoglobulin G(blood); Mice; Molecular Weight; Neurons(cytology; drug effects); Neuroprotective Agents(immunology); Peptides(chemistry; immunology); Primates(immunology); Protein Processing, Post-Translational(drug effects); Protein Structure, Quaternary
Curation Last Updated:2016-04-05 22:46:19