Mruthinti, S. et al. Autoimmunity in Alzheimer's disease: increased levels of circulating IgGs binding Aβ and RAGE peptides. Neurobiol. Aging 25, 1023-1032
ABSTRACT 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.
- SourceAvailable from: Rodrigo Lorenzi
[Show abstract] [Hide abstract]
- "Recently, autoantibodies directed against sRAGE were found to be increased in Alzheimer's disease and rheumatoid arthritis  . Our group has also observed increased levels of antisRAGE autoantibodies in haemodialysis patients that might be associated with uraemic vascular dysfunction and with increased sRAGE levels . "
ABSTRACT: Morbid obesity increases the risk of cardiovascular disease (CVD). The receptor for advanced glycation end-products (RAGE) is implicated in proinflammatory processes that underlie CVD. Its soluble form (sRAGE) has been proposed as a vascular biomarker. Recently, anti-sRAGE autoantibodies were described and found to be increased in diseases where RAGE is overexpressed. This study aimed to investigate serum levels of anti-sRAGE autoantibodies in morbidly obese patients.Diabetes & Metabolism 06/2014; 40(5). DOI:10.1016/j.diabet.2014.04.008
The Clinical Spectrum of Alzheimer's Disease -The Charge Toward Comprehensive Diagnostic and Therapeutic Strategies, 09/2011; , ISBN: 978-953-307-993-6
- "Although antibody production is a B cell-dependent process, the response is supported by activated T cells. At least three studies to date found increased levels of circulating Abeta auto-antibodies in patients clinically diagnosed with dementia compared to non-demented controls (Nath, Hall et al. 2003) (Gruden, Davudova et al. 2004) (Mruthinti, Buccafusco et al. 2004). Using various peptides and specific assay systems to stimulate peripheral T cells from AD patients, it was also demonstrated that T cells specific for the fragment 1-42 of the Abeta peptide (Abeta1- 42) can be detected in peripheral blood (Monsonego, Zota et al. 2003). "
[Show abstract] [Hide abstract]
- "Plasma: 82 AD, 271 NCI No differences between groups (ELISA) Weksler et al., 2002 Serum: 19 AD, 33 NCI Decreased AD anti-Ab levels (ELISA) Nath et al., 2003 Serum: 16 AD, 31 NCI Anti-Ab higher in AD patients Gruden et al., 2004 Serum: 17 AD, 15 NCI Increased anti-Ab25-35 oligomer antibodies in AD patients (ELISA) Baril et al., 2004 Serum: 36 AD, 34 NCI No differences between groups (ELISA) Mruthinti et al., 2004 Plasma: 33 AD, 42 NCI Anti-Ab antibodies significantly (4-fold) increased in AD plasma (ELISA) Moir et al., 2005 Plasma: 59 AD, 59 NCI No differences for anti-Ab monomer antibodies; decreased AD levels for anti-Ab oligomer levels (ELISA) Brettschneider et al., 2005 Serum: 96 AD, 30 NCI Anti-Ab levels decreased in AD (immunoprecipitation assay) Jianping et al., 2006 Serum: 20 AD, 20 NCI Decreased AD anti-Ab levels (ELISA) and avidity Song et al., 2007 Serum: 153 AD, 193 NCI Decreased AD anti-Ab levels (ELISA) Gruden et al., 2007 Serum: 48 AD, 28 NCI Increased anti-Ab25-35 oligomer antibodies in AD patients (ELISA, dot blot) Gustaw et al., 2008 Serum: 23 or 35 AD (assays performed in two laboratories), 35 NCI Anti-Ab levels consistently increased in AD vs. controls only after dissociation Xu et al., 2008 Plasma: 113 AD, 205 NCI No differences between groups (plaque immunoreactivity) Britschgi et al., 2009 Plasma: 75 AD, 36 NCI No differences between groups (Ab microarrays) Sohn et al., 2009 Serum: 136 AD, 210 NCI Anti-Ab decreased in AD patients (ELISA) "
ABSTRACT: The literature contains conflicting results regarding the status of serum anti-Aβ antibody concentrations in Alzheimer's disease (AD). Reduced levels of these antibodies have been suggested to contribute to the development of this disorder. The conflicting results may be due to polyvalent antibodies, antibody "masking" due to Aβ binding, methodological differences, and/or small sample sizes. The objectives of this pilot study were to compare serum anti-Aβ antibody concentrations between AD, mild cognitive impairment (MCI), and elderly noncognitively impaired (NCI) subjects while addressing these issues, and to perform power analyses to determine appropriate group sizes for future studies employing this approach. Serum antibodies to Aβ1-42 monomer and soluble oligomers in AD, MCI, and NCI subjects (10/group) were measured by ELISA, subtracting polyvalent antibody binding and dissociating antibody-antigen complexes. Differences in mean antibody levels were assessed for significance with repeated measures ANOVA using restricted maximum likelihood estimation, using Tukey-Kramer tests and confidence intervals for multiple comparisons. Spearman's rank correlation was used to determine associations between anti-monomer and anti-oligomer antibody concentrations. Estimated sample sizes required to detect effects of various sizes were calculated. There were no significant differences between groups for mean anti-Aβ antibody levels, although these tended to be higher in AD than NCI specimens. Estimated group sizes of 328 and 150 for anti-Aβ monomer and oligomer antibodies, respectively, would have been required for 80% power for significance at 0.05 for a 25% increase in the AD mean relative to the NCI mean. Serum antibody concentrations to Aβ monomer and oligomers were strongly associated (correlations: 0.798 for undissociated sera, 0.564 for dissociated sera). Antibody-antigen dissociation significantly increased anti-Aβ monomer but not anti-Aβ oligomer antibody levels. The findings in this pilot study are consistent with relatively similar concentrations of specific, non-antigen-bound antibodies to Aβ1-42 monomer and soluble oligomers in AD, MCI, and NCI sera. The differences between groups for these antibodies would have required approximate group sizes of 328 and 150, respectively, for a high probability for statistical significance. These findings do not support the hypothesis that reduced levels of anti-Aβ antibodies might contribute to AD's pathogenesis.Journal of Neuroinflammation 08/2011; 8:93. DOI:10.1186/1742-2094-8-93