Immune complexes of auto-antibodies against A beta 1-42 peptides patrol cerebrospinal fluid of non-Alzheimer's patients.
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.
Henkel
A W
AW
Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany.
Dittrich
P S
PS
Groemer
T W
TW
Lemke
E A
EA
Klingauf
J
J
Klafki
H W
HW
Lewczuk
P
P
Esselmann
H
H
Schwille
P
P
Kornhuber
J
J
Wiltfang
J
J
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
D016229:Amyloid beta-Peptides; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)