Anti-RAGE and Aβ immunoglobulin levels are related to dementia level and cognitive performance

Jennifer S. Wilson, Shyamala Mruthinti, Jerry J. Buccafusco, Rosann F. Schade, Meghan B. Mitchell, Dean U. Harrell, Nidhi K. Gulati, L. Stephen Miller

Research output: Contribution to journalArticle

24 Citations (Scopus)

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-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.

Original languageEnglish (US)
Pages (from-to)264-271
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume64
Issue number2
DOIs
StatePublished - Feb 1 2009

Fingerprint

Dementia
Immunoglobulins
Immunoglobulin G
Alzheimer Disease
Language
Repression (Psychology)
Peptide Receptors
Amyloid beta-Peptides
Amyloid Plaques
Advanced Glycosylation End Product-Specific Receptor
Referral and Consultation
Biomarkers
Regression Analysis
Physicians
Brain

Keywords

  • Alzheimer's disease
  • Biomarker
  • Cognition
  • Dementia
  • Immunoglobulin
  • RAGE

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Anti-RAGE and Aβ immunoglobulin levels are related to dementia level and cognitive performance. / Wilson, Jennifer S.; Mruthinti, Shyamala; Buccafusco, Jerry J.; Schade, Rosann F.; Mitchell, Meghan B.; Harrell, Dean U.; Gulati, Nidhi K.; Miller, L. Stephen.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 64, No. 2, 01.02.2009, p. 264-271.

Research output: Contribution to journalArticle

Wilson, Jennifer S. ; Mruthinti, Shyamala ; Buccafusco, Jerry J. ; Schade, Rosann F. ; Mitchell, Meghan B. ; Harrell, Dean U. ; Gulati, Nidhi K. ; Miller, L. Stephen. / Anti-RAGE and Aβ immunoglobulin levels are related to dementia level and cognitive performance. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2009 ; Vol. 64, No. 2. pp. 264-271.
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AU - Mruthinti, Shyamala

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AU - Schade, Rosann F.

AU - Mitchell, Meghan B.

AU - Harrell, Dean U.

AU - Gulati, Nidhi K.

AU - Miller, L. Stephen

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N2 - 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.

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