title: Immune complexes of auto-antibodies against A beta 1-42 peptides patrol cerebrospinal fluid of non-Alzheimer's patients.
abstract: The diagnostic potential of large A beta-peptide binding particles (LAPs) in the cerebrospinal fluid (CSF) of Alzheimer's dementia (AD) patients and non-AD controls (nAD) was evaluated. LAPs were detected by confocal spectroscopy in both groups with high inter-individual variation in number. Molecular imaging by confocal microscopy revealed that LAPs are heterogeneous superaggregates that could be subdivided morphologically into four main types (LAP 1-4). LAP-4 type, resembling a 'large chain of pearls', was detected in 42.1% of all nAD controls but it was virtually absent in AD patients. LAP-4 type could be selectively removed by protein A beads, a clear indication that it contained immunoglobulins in addition to beta-amyloid peptides (A beta 1-42). We observed a close correlation between LAPs and immunoglobulin G (IgG) concentration in CSF in controls but not in AD patients. Double labeling of LAPs with anti-A beta and anti-IgG antibodies confirmed that LAP-4 type consisted of A beta and IgG aggregates. Our results assign a central role to the immune system in regulating A beta1-42 homeostasis by clustering this peptide in immunocomplexes.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: A W
authors.initials: AW
authors.lastname: Henkel
authors.forename: P S
authors.initials: PS
authors.lastname: Dittrich
authors.forename: T W
authors.initials: TW
authors.lastname: Groemer
authors.forename: E A
authors.initials: EA
authors.lastname: Lemke
authors.forename: J
authors.initials: J
authors.lastname: Klingauf
authors.forename: H W
authors.initials: HW
authors.lastname: Klafki
authors.forename: P
authors.initials: P
authors.lastname: Lewczuk
authors.forename: H
authors.initials: H
authors.lastname: Esselmann
authors.forename: P
authors.initials: P
authors.lastname: Schwille
authors.forename: J
authors.initials: J
authors.lastname: Kornhuber
authors.forename: J
authors.initials: J
authors.lastname: Wiltfang
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000134:cerebrospinal fluid*; D001323:Autoantibodies / Q000134:cerebrospinal fluid* / Q000145:classification; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D002490:Central Nervous System / Q000276:immunology; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000145:classification / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid* / Q000276:immunology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000276:immunology*; D012016:Reference Values
chemical_list: D016229:Amyloid beta-Peptides; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)