The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access published online on February 5, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, doi:10.1093/gerona/gln002
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Anti-RAGE and Aβ Immunoglobulin Levels Are Related to Dementia Level and Cognitive Performance
1 Department of Psychology, University of Georgia, Athens
2 Charlie Norwood VA Medical Center, Augusta, Georgia
3 Department of Pharmacology and Toxicology
4 Alzheimer's Research Center
5 Department of Internal Medicine
6 Department of Family Medicine, Medical College of Georgia, Augusta
7 Georgia War Veterans Nursing Home, Department of Family Medicine, Augusta
Address correspondence to L. Stephen Miller, PhD, 110 Hooper Street, Psychology Building Room 163, University of Georgia, Athens, GA 30602-3013. Email: lsmiller{at}uga.edu
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Abstract |
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Background: Blood-based immunoglobulins (IgGs) may mark the presence of amyloid plaques characterizing the progression of Alzheimer's disease (AD). Previous studies suggest that anti-RAGE and anti-Aβ IgGs increase proportionately with accumulation of amyloid-beta (Aβ) peptides at receptor sites for advanced glycation end products (RAGE), within cortical areas of brain tissue. We assessed the relationship between these potential markers and an AD-type cognitive profile. We hypothesized that these specific IgG levels would be positively correlated with Clinical Dementia Rating (CDR) scores as well as index scores on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in domains associated with cortical function.
Methods: Participants were 118 older adults (mean age = 74, standard deviation = 10.5) drawn from the community and local physician referrals. Participants were reassigned into five groups based on CDR. Blood IgG levels were determined through an affinity purification process.
Results: Analysis of covariance analyses revealed that CDR scores were significantly related to anti-RAGE, F(4,106) = 12.93, p < .001, and anti-Aβ, F(4,106) = 17.08, p < .001, after controlling for age and total IgG levels. Regression analyses indicated significant variance accounted for by anti-RAGE and anti-Aβ above and beyond total IgG effects. Additional regression identified specific RBANS domains accounting for significant variance in anti-RAGE levels including language (t = –3.74, p < .001) and delayed memory (t = –2.31, p < .05), whereas language accounted for a significant amount of variance in anti-Aβ levels (t = –3.96, p < .001).
Conclusions: Anti-RAGE and anti-Aβ IgGs correlate strongly with global scores of dementia. Furthermore, they are associated with a profile of deficiency in domains associated with specific cortical function. Results suggest potential for anti-Aβ and anti-RAGE IgGs as blood biomarkers for AD.
Keywords Dementia; Alzheimer's disease; Biomarker; RAGE; Aβ; Immunoglobulin; Cognition
Received: May 16, 2007; Accepted: April 3, 2008