Increased Levels of Antigen-Bound β-Amyloid Autoantibodies in Serum and Cerebrospinal Fluid of Alzheimer’s Disease Patients

Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer's disease (AD). However, the determination of both free and dissociated Aβ-autoantibodies in serum hitherto has yielded inconsistent results regarding their function and po...

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Published inPloS one Vol. 8; no. 7; p. e68996
Main Authors Maftei, Madalina, Thurm, Franka, Schnack, Cathrin, Tumani, Hayrettin, Otto, Markus, Elbert, Thomas, Kolassa, Iris-Tatjana, Przybylski, Michael, Manea, Marilena, von Arnim, Christine A. F.
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 18.07.2013
Public Library of Science (PLoS)
Subjects
Aged
Alzheimer Disease - immunology
Alzheimer's disease
Amyloid beta-Peptides - immunology
Analytical chemistry
Antibody Specificity
Antigen-antibody complexes
Antigens
Apolipoproteins
Autoantibodies
Autoantibodies - blood
Autoantibodies - cerebrospinal fluid
Biology
Biomarkers
Biopolymers
Cerebrospinal fluid
Chemistry
Clinical trials
Cognition - physiology
Cognitive ability
Dementia
Enzyme-linked immunosorbent assay
Enzyme-Linked Immunosorbent Assay - methods
Epitopes - genetics
Female
Humans
Immune clearance
Immune response
Immune system
Immunization
Immunoglobulin G
Immunoglobulin G - blood
Immunoglobulin G - cerebrospinal fluid
Immunoglobulins
Immunotherapy
In vivo methods and tests
Laboratories
Male
Medicine
Middle Aged
Models, Statistical
Neurodegenerative diseases
Neurology
Patients
Peptides
Plasma
Proteins
Rodents
β-Amyloid
Germany
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Abstract Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer's disease (AD). However, the determination of both free and dissociated Aβ-autoantibodies in serum hitherto has yielded inconsistent results regarding their function and possible biomarker value. Here we report the application of a new sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of antigen-bound Aβ-autoantibodies (intact Aβ-IgG immune complexes) in serum and cerebrospinal fluid (CSF) of a total number of 112 AD patients and age- and gender-matched control subjects. Both serum and CSF levels of Aβ-IgG immune complexes were found to be significantly higher in AD patients compared to control subjects. Moreover, the levels of Aβ-IgG complexes were negatively correlated with the cognitive status across the groups, increasing with declining cognitive test performance of the subjects. Our results suggest a contribution of IgG-type autoantibodies to Aβ clearance in vivo and an increased immune response in AD, which may be associated with deficient Aβ-IgG removal. These findings may contribute to elucidating the role of Aβ-autoantibodies in AD pathophysiology and their potential application in AD diagnosis.
AbstractList Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer's disease (AD). However, the determination of both free and dissociated Aβ-autoantibodies in serum hitherto has yielded inconsistent results regarding their function and possible biomarker value. Here we report the application of a new sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of antigen-bound Aβ-autoantibodies (intact Aβ-IgG immune complexes) in serum and cerebrospinal fluid (CSF) of a total number of 112 AD patients and age- and gender-matched control subjects. Both serum and CSF levels of Aβ-IgG immune complexes were found to be significantly higher in AD patients compared to control subjects. Moreover, the levels of Aβ-IgG complexes were negatively correlated with the cognitive status across the groups, increasing with declining cognitive test performance of the subjects. Our results suggest a contribution of IgG-type autoantibodies to Aβ clearance in vivo and an increased immune response in AD, which may be associated with deficient Aβ-IgG removal. These findings may contribute to elucidating the role of Aβ-autoantibodies in AD pathophysiology and their potential application in AD diagnosis.
Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer’s disease (AD). However, the determination of both free and dissociated Aβ-autoantibodies in serum hitherto has yielded inconsistent results regarding their function and possible biomarker value. Here we report the application of a new sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of antigen-bound Aβ-autoantibodies (intact Aβ-IgG immune complexes) in serum and cerebrospinal fluid (CSF) of a total number of 112 AD patients and age- and gender-matched control subjects. Both serum and CSF levels of Aβ-IgG immune complexes were found to be significantly higher in AD patients compared to control subjects. Moreover, the levels of Aβ-IgG complexes were negatively correlated with the cognitive status across the groups, increasing with declining cognitive test performance of the subjects. Our results suggest a contribution of IgG-type autoantibodies to Aβ clearance in vivo and an increased immune response in AD, which may be associated with deficient Aβ-IgG removal. These findings may contribute to elucidating the role of Aβ-autoantibodies in AD pathophysiology and their potential application in AD diagnosis.
Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer's disease (AD). However, the determination of both free and dissociated Aβ-autoantibodies in serum hitherto has yielded inconsistent results regarding their function and possible biomarker value. Here we report the application of a new sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of antigen-bound Aβ-autoantibodies (intact Aβ-IgG immune complexes) in serum and cerebrospinal fluid (CSF) of a total number of 112 AD patients and age- and gender-matched control subjects. Both serum and CSF levels of Aβ-IgG immune complexes were found to be significantly higher in AD patients compared to control subjects. Moreover, the levels of Aβ-IgG complexes were negatively correlated with the cognitive status across the groups, increasing with declining cognitive test performance of the subjects. Our results suggest a contribution of IgG-type autoantibodies to Aβ clearance in vivo and an increased immune response in AD, which may be associated with deficient Aβ-IgG removal. These findings may contribute to elucidating the role of Aβ-autoantibodies in AD pathophysiology and their potential application in AD diagnosis.Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer's disease (AD). However, the determination of both free and dissociated Aβ-autoantibodies in serum hitherto has yielded inconsistent results regarding their function and possible biomarker value. Here we report the application of a new sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of antigen-bound Aβ-autoantibodies (intact Aβ-IgG immune complexes) in serum and cerebrospinal fluid (CSF) of a total number of 112 AD patients and age- and gender-matched control subjects. Both serum and CSF levels of Aβ-IgG immune complexes were found to be significantly higher in AD patients compared to control subjects. Moreover, the levels of Aβ-IgG complexes were negatively correlated with the cognitive status across the groups, increasing with declining cognitive test performance of the subjects. Our results suggest a contribution of IgG-type autoantibodies to Aβ clearance in vivo and an increased immune response in AD, which may be associated with deficient Aβ-IgG removal. These findings may contribute to elucidating the role of Aβ-autoantibodies in AD pathophysiology and their potential application in AD diagnosis.
Author Tumani, Hayrettin
Kolassa, Iris-Tatjana
Elbert, Thomas
von Arnim, Christine A. F.
Thurm, Franka
Przybylski, Michael
Manea, Marilena
Schnack, Cathrin
Otto, Markus
Maftei, Madalina
AuthorAffiliation 3 Department of Psychology, University of Konstanz, Konstanz, Germany
6 Department of Neurology, University of Ulm, Ulm, Germany
Julius-Maximilians-Universität Würzburg, Germany
5 Department of Psychology, TU Dresden, Dresden, Germany
2 Steinbeis Research Center for Biopolymer Analysis, University of Konstanz, Konstanz, Germany
1 Laboratory of Analytical Chemistry and Biopolymer Structure Analysis, Department of Chemistry, University of Konstanz, Konstanz, Germany
7 Zukunftskolleg, University of Konstanz, Konstanz, Germany
4 Clinical and Biological Psychology, Institute of Psychology and Education, University of Ulm, Ulm, Germany
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– name: 4 Clinical and Biological Psychology, Institute of Psychology and Education, University of Ulm, Ulm, Germany
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– name: 5 Department of Psychology, TU Dresden, Dresden, Germany
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Copyright 2013 Maftei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2013 Maftei et al 2013 Maftei et al
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: CAFVA M. Manea I-TK MP TE M. Maftei. Performed the experiments: M. Maftei M. Manea. Analyzed the data: FT M. Maftei CS M. Manea MP CAFVA I-TK HT MO. Wrote the paper: FT M. Maftei M. Manea CAFVA MP I-TK. Critically revised the manuscript: FT M. Maftei CS M. Manea MP CAFVA I-TK TE HT MO. Approved the final version of the manuscript: FT M. Maftei CS M. Manea MP CAFVA I-TK TE HT MO.
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Snippet Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer's disease (AD). However, the...
Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer’s disease (AD). However, the...
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StartPage e68996
SubjectTerms Aged
Alzheimer Disease - immunology
Alzheimer's disease
Amyloid beta-Peptides - immunology
Analytical chemistry
Antibody Specificity
Antigen-antibody complexes
Antigens
Apolipoproteins
Autoantibodies
Autoantibodies - blood
Autoantibodies - cerebrospinal fluid
Biology
Biomarkers
Biopolymers
Cerebrospinal fluid
Chemistry
Clinical trials
Cognition - physiology
Cognitive ability
Dementia
Enzyme-linked immunosorbent assay
Enzyme-Linked Immunosorbent Assay - methods
Epitopes - genetics
Female
Humans
Immune clearance
Immune response
Immune system
Immunization
Immunoglobulin G
Immunoglobulin G - blood
Immunoglobulin G - cerebrospinal fluid
Immunoglobulins
Immunotherapy
In vivo methods and tests
Laboratories
Male
Medicine
Middle Aged
Models, Statistical
Neurodegenerative diseases
Neurology
Patients
Peptides
Plasma
Proteins
Rodents
β-Amyloid
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Title Increased Levels of Antigen-Bound β-Amyloid Autoantibodies in Serum and Cerebrospinal Fluid of Alzheimer’s Disease Patients
URI https://www.ncbi.nlm.nih.gov/pubmed/23874844
https://www.proquest.com/docview/1427370336
https://www.proquest.com/docview/1411633218
https://pubmed.ncbi.nlm.nih.gov/PMC3715516
https://doaj.org/article/df3f3cdbb22f41d5b125f44dc63be507
http://dx.doi.org/10.1371/journal.pone.0068996
Volume 8
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