title: Anti-RAGE and Abeta immunoglobulin levels are related to dementia level and cognitive performance.
abstract: 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-Abeta IgGs increase proportionately with accumulation of amyloid-beta (Abeta) 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-Abeta, 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-Abeta 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-Abeta levels (t = -3.96, p < .001).
  
  
  CONCLUSIONS
  Anti-RAGE and anti-Abeta 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-Abeta and anti-RAGE IgGs as blood biomarkers for AD.
authors.affiliation: University of Georgia, 110 Hooper Street, Athens, GA 30602-3013, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Wilson
authors.forename: Shyamala
authors.initials: S
authors.lastname: Mruthinti
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Buccafusco
authors.forename: Rosann F
authors.initials: RF
authors.lastname: Schade
authors.forename: Meghan B
authors.initials: MB
authors.lastname: Mitchell
authors.forename: Dean U
authors.initials: DU
authors.lastname: Harrell
authors.forename: Nidhi K
authors.initials: NK
authors.lastname: Gulati
authors.forename: L Stephen
authors.initials: LS
authors.lastname: Miller
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood* / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000097:blood / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D003072:Cognition Disorders / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D015331:Cohort Studies; D003704:Dementia / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D011336:Probability; D011379:Prognosis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000097:blood* / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012737:Sex Factors
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D007074:Immunoglobulin G; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic