Autoimmunity in Alzheimer’s disease: increased levels of circulating IgGs binding Aβ and RAGE peptides
| Autor: | Shyamala Mruthinti, William D. Hill, Thomas W. Jackson, Jerry J. Buccafusco, Edward Zamrini, Rosann F. Schade, Jennifer L. Waller |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Aging medicine.medical_specialty Amyloid medicine.drug_class Receptor for Advanced Glycation End Products medicine.disease_cause Monoclonal antibody Epitope Autoimmune Diseases Autoimmunity RAGE (receptor) Epitopes Alzheimer Disease Internal medicine Leukocytes medicine Amyloid precursor protein Humans Receptors Immunologic Aged Amyloid beta-Peptides Binding Sites biology Chemistry General Neuroscience Antibodies Monoclonal Middle Aged medicine.disease Peptide Fragments Up-Regulation Endocrinology Immunoglobulin G Antigens Surface Immunology biology.protein Encephalitis Female Neurology (clinical) Geriatrics and Gerontology Antibody Alzheimer's disease Developmental Biology |
| Zdroj: | Neurobiology of Aging. 25:1023-1032 |
| ISSN: | 0197-4580 |
| Popis: | Plasma samples derived from 33 Alzheimer's disease (AD) and 42 control participants were subjected to several steps to purify specific anti-(amyloid)Abeta IgGs. Affinity-purified IgGs binding the peptide Abeta1-42, a neurotoxic sequence derived from the trans-membrane amyloid precursor protein, exhibited nearly four-fold higher titers in AD patients compared with their control non-AD cohort. Affinity-purified IgGs binding a fragment of the receptor for advanced glycation end products (RAGE) likewise were increased nearly three-fold in AD individuals. Abeta and RAGE IgG titers were negatively correlated with cognitive status, i.e. the more cognitively impaired individuals tended to exhibit higher IgG titers. Abeta IgG titers were negatively correlated with age in the control group, but not with the AD group. Levels of circulating AB- and RAGE-like proteins were not different between AD and control participants, nor was there a relationship between individual IgG titers and the respective Abeta- and RAGE-like proteins. Freshly prepared leukocyte preparations were subjected to flow cytometric analysis. AD individuals exhibited significantly increased populations of cells expressing binding sites for monoclonal antibodies directed against Abeta (5.5-fold), betaAPP (3.5-fold), and RAGE (2.6-fold) relative to the control group. These findings confirm the presence of circulating IgGs specifically directed at proteins implicated in immunological processes linked to AD. The close relationship between titers for Abeta and RAGE IgGs suggests the possibility that the antibodies are being produced in response to a common mechanism or protein complex (with the respective epitopes) linked to the disease. |
| Databáze: | OpenAIRE |
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