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.
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: R C Dodel; Y Du; C Depboylu; H Hampel; L Frölich; A Haag; U Hemmeter; S Paulsen; S J Teipel; S Brettschneider; A Spottke; C Nölker; H J Möller; X Wei; M Farlow; N Sommer; W H Oertel Journal: J Neurol Neurosurg Psychiatry Date: 2004-10 Impact factor: 10.154
Authors: S Du Yan; H Zhu; J Fu; S F Yan; A Roher; W W Tourtellotte; T Rajavashisth; X Chen; G C Godman; D Stern; A M Schmidt Journal: Proc Natl Acad Sci U S A Date: 1997-05-13 Impact factor: 11.205
Authors: H A Crystal; D W Dickson; M J Sliwinski; R B Lipton; E Grober; H Marks-Nelson; P Antis Journal: Ann Neurol Date: 1993-10 Impact factor: 10.422
Authors: Avindra Nath; Elizabeth Hall; Marnia Tuzova; Michael Dobbs; Melina Jons; Caroline Anderson; Jerold Woodward; Zhihong Guo; Weiming Fu; Richard Kryscio; David Wekstein; Charles Smith; William R Markesbery; Mark P Mattson Journal: Neuromolecular Med Date: 2003 Impact factor: 3.843
Authors: Scott J Webster; Shyamala Mruthinti; William David Hill; Jerry J Buccafusco; Alvin V Terry Journal: Neuromolecular Med Date: 2012-03-14 Impact factor: 3.843
Authors: Fang Fang; Lih-Fen Lue; Shiqiang Yan; Hongwei Xu; John S Luddy; Doris Chen; Douglas G Walker; David M Stern; Shifang Yan; Ann Marie Schmidt; John X Chen; Shirley ShiDu Yan Journal: FASEB J Date: 2009-11-11 Impact factor: 5.191